Publications by category
Books
Schrader TA, Carmichael R, Schrader M (2023). Immunolabelling for detection of endogenous and overexpressed peroxisomal proteins in mammalian cells., Springer.
Journal articles
Azadi AS, Carmichael RE, Kovacs WJ, Koster J, Kors S, Waterham HR, Schrader M (In Press). A functional SMAD2/3 binding site in the PEX11β promoter identifies a role for TGFβ in peroxisome proliferation in humans. Frontiers in Cell and Developmental Biology
Schrader M, Carmichael R (In Press). Determinants of peroxisome membrane dynamics. Frontiers in Physiology
Carmichael RE, Islinger M, Schrader M (In Press). Fission Impossible (?) – New Insights into Disorders of Peroxisome Dynamics. Cells
Soares Carneiro Da Silva B, DiGiovanni L, Kumar R, Carmichael RE, Kim PK, Schrader M (In Press). Maintaining social contacts: the physiological relevance of organelle interactions. BBA: Molecular Cell Research
Passmore J, Carmichael R, Schrader T, Godinho L, Ferdinandusse S, Lismont C, Wang Y, Hacker C, Islinger M, Fransen M, et al (In Press). Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation. BBA: Molecular Cell Research
Carmichael R, Richards D, Fahimi HD, Schrader M (In Press). Organelle Membrane Extensions in Mammalian Cells. Biology
Schrader T, Carmichael R, Islinger M, Costello J, Hacker C, Bonekamp N, Weishaupt J, Andersen P, Schrader M (In Press). PEX11β and FIS1 cooperate in peroxisome division independent of Mitochondrial Fission Factor. Journal of Cell Science
Silva B, Schrader TA, Schrader M, Carmichael R (2023). Generation of reporter cell lines for endogenous expression analysis of peroxisomal proteins. Methods in Molecular Biology
Schrader T, Carmichael R, Schrader M (2023). Immunolabelling for detection of endogenous and overexpressed peroxisomal proteins in mammalian cells. Methods in Molecular Biology
Soares ES, de Souza ACG, Zanella CA, Carmichael RE, Henley JM, Wilkinson KA, Cimarosti HI (2022). Effects of amyloid-β on protein SUMOylation and levels of mitochondrial proteins in primary cortical neurons. IBRO Neuroscience Reports, 12, 142-148.
Angelika T, Carmichael R (2022). First person - Tina Angelika Schrader and Ruth Carmichael.
JOURNAL OF CELL SCIENCE,
135(13).
Author URL.
Waters E, Wilkinson KA, Harding AL, Carmichael RE, Robinson D, Colley HE, Guo C (2022). The SUMO protease SENP3 regulates mitochondrial autophagy mediated by Fis1.
EMBO REPORTS,
23(2).
Author URL.
McMillan KJ, Banks PJ, Hellel FLN, Carmichael RE, Clairfeuille T, Evans AJ, Heesom KJ, Lewis P, Collins BM, Bashir ZI, et al (2021). Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2.
eLife,
10Abstract:
Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2
The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through sorting of integral proteins to the synaptic surface, most notably AMPA receptors. To provide a broader view of SNX27-associated pathologies, we performed proteomics in rat primary neurons to identify SNX27-dependent cargoes, and identified proteins linked to excitotoxicity, epilepsy, intellectual disabilities, and working memory deficits. Focusing on the synaptic adhesion molecule LRFN2, we established that SNX27 binds to LRFN2 and regulates its endosomal sorting. Furthermore, LRFN2 associates with AMPA receptors and knockdown of LRFN2 results in decreased surface AMPA receptor expression, reduced synaptic activity, and attenuated hippocampal long-term potentiation. Overall, our study provides an additional mechanism by which SNX27 can control AMPA receptor-mediated synaptic transmission and plasticity indirectly through the sorting of LRFN2 and offers molecular insight into the perturbed function of SNX27 and LRFN2 in a range of neurological conditions.
Abstract.
Passmore JB, Godinho LF, Ferdinandusse S, Lismont C, Wang Y, Hacker C, Islinger M, Fransen M, Richards DM, Freisinger P, et al (2020). Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation.
bioRxiv, 2020.01.08.898486-2020.01.08.898486.
Abstract:
Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation
Peroxisomes are highly dynamic subcellular compartments with important functions in lipid and ROS metabolism. Impaired peroxisomal function can lead to severe metabolic disorders with developmental defects and neurological abnormalities. Recently, a new group of disorders has been identified, characterised by defects in the membrane dynamics and division of peroxisomes rather than by loss of metabolic functions. However, the contribution of impaired peroxisome plasticity to the pathophysiology of those disorders is not well understood. Mitochondrial fission factor (MFF) is a key component of both the peroxisomal and mitochondrial division machinery. Patients with MFF deficiency present with developmental and neurological abnormalities. Peroxisomes (and mitochondria) in patient fibroblasts are highly elongated as a result of impaired organelle division. The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown. Here, we show that MFF deficiency does not cause alterations to overall peroxisomal biochemical function. However, loss of MFF results in reduced import-competency of the peroxisomal compartment and leads to the accumulation of pre-peroxisomal membrane structures. We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH as well as altered distribution in neuronal cells. Removal of elongated peroxisomes through induction of autophagic processes is not impaired. A mathematical model describing key processes involved in peroxisome dynamics sheds further light into the physical processes disturbed in MFF-deficient cells. The consequences of our findings for the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity are discussed. ACOX1 :. acyl-CoA oxidase 1; PBD :. peroxisome biogenesis disorder; PED :. single peroxisomal enzyme deficiency; DRP1 :. dynamin-related protein 1; ER :. endoplasmic reticulum; FIS1 :. mitochondrial fission 1 protein; MFF :. Mitochondrial fission factor; ROS :. reactive oxygen species; PTS :. peroxisome targeting signal; VLCFA :. very-long-chain fatty acid.
Abstract.
Carmichael RE, Wilkinson KA, Craig TJ (2019). Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes.
Scientific Reports,
9(1).
Abstract:
Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes
Type-II Diabetes Mellitus (T2DM) is one of the fastest growing public health issues today, consuming 12% of worldwide health budgets and affecting an estimated 400 million people. One of the key pathological traits of this disease is insulin resistance at ‘glucose sink’ tissues (mostly skeletal muscle), and this remains one of the features of this disease most intractable to therapeutic intervention. Several lines of evidence have implicated the post-translational modification, SUMOylation, in insulin signalling and insulin resistance in skeletal muscle. In this study, we examined this possibility by manipulation of cellular SUMOylation levels using multiple different tools, and assaying the effect on insulin-stimulated GLUT4 surface expression in differentiated L6 rat myocytes. Although insulin stimulation of L6 myocytes produced a robust decrease in total cellular SUMO1-ylation levels, manipulating cellular SUMOylation had no effect on insulin-responsive GLUT4 surface trafficking using any of the tools we employed. Whilst we cannot totally exclude the possibility that SUMOylation plays a role in the insulin signalling pathway in human health and disease, our data strongly argue that GLUT4 trafficking in response to insulin is not regulated by protein SUMOylation, and that SUMOylation does not therefore represent a viable therapeutic target for the treatment of insulin resistance.
Abstract.
Davey JS, Carmichael RE, Craig TJ (2019). Protein SUMOylation regulates insulin secretion at multiple stages.
Scientific Reports,
9(1).
Abstract:
Protein SUMOylation regulates insulin secretion at multiple stages
Type-II Diabetes Mellitus (T2DM) is one of the fastest growing public health issues of modern times, consuming 12% of worldwide health budgets and affecting an estimated 400 million people. A key pathological trait associated with this disease is the failure of normal glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells. Several lines of evidence suggest that vesicle trafficking events such as insulin secretion are regulated by the post-translational modification, SUMOylation, and indeed SUMOylation has been proposed to act as a ‘brake’ on insulin exocytosis. Here, we show that diabetic stimuli which inhibit GSIS are correlated with an increase in cellular protein SUMOylation, and that inhibition of deSUMOylation reduces GSIS. We demonstrate that manipulation of cellular protein SUMOylation levels, by overexpression of several different components of the SUMOylation pathway, have varied and complex effects on GSIS, indicating that SUMOylation regulates this process at multiple stages. We further demonstrate that inhibition of syntaxin1A SUMOylation, via a knockdown-rescue strategy, greatly enhances GSIS. Our data are therefore consistent with the model that SUMOylation acts as a brake on GSIS, and we have identified SUMOylation of syntaxin 1 a as a potential component of this brake. However, our data also demonstrate that the role of SUMOylation in GSIS is complex and may involve many substrates.
Abstract.
Henley JM, Carmichael RE, Wilkinson KA (2018). Extranuclear SUMOylation in Neurons.
Trends in Neurosciences,
41(4), 198-210.
Abstract:
Extranuclear SUMOylation in Neurons
Post-translational modification of substrate proteins by SUMO conjugation regulates a diverse array of cellular processes. While predominantly a nuclear protein modification, there is a growing appreciation that SUMOylation of proteins outside the nucleus plays direct roles in controlling synaptic transmission, neuronal excitability, and adaptive responses to cell stress. Furthermore, alterations in protein SUMOylation are observed in a wide range of neurological and neurodegenerative diseases, and several extranuclear disease-associated proteins have been shown to be directly SUMOylated. Here, focusing mainly on SUMOylation of synaptic and mitochondrial proteins, we outline recent developments and discoveries, and present our opinion as to the most exciting avenues for future research to define how SUMOylation of extranuclear proteins regulates neuronal and synaptic function.
Abstract.
Carmichael RE, Wilkinson KA, Craig TJ, Ashby MC, Henley JM (2018). MEF2A regulates mGluR-dependent AMPA receptor trafficking independently of Arc/Arg3.1.
SCIENTIFIC REPORTS,
8 Author URL.
Zhu B, Carmichael RE, Valois LS, Wilkinson KA, Henley JM (2018). The transcription factor MEF2A plays a key role in the differentiation/ maturation of rat neural stem cells into neurons.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,
500(3), 645-649.
Author URL.
Carmichael RE, Henley JM (2018). Transcriptional and post-translational regulation of Arc in synaptic plasticity.
Seminars in Cell and Developmental Biology,
77, 3-9.
Abstract:
Transcriptional and post-translational regulation of Arc in synaptic plasticity
One of the most interesting features of Arc-dependent synaptic plasticity is how multiple types of synaptic activity can converge to alter Arc transcription and then diverge to induce different plasticity outcomes, ranging from AMPA receptor internalisation that promotes long-term depression (LTD), to actin stabilisation that promotes long-term potentiation (LTP). This diversity suggests that there must be numerous levels of control to ensure the temporal profile, abundance, localisation and function of Arc are appropriately regulated to effect learning and memory in the correct contexts. The activity-dependent transcription and post-translational modification of Arc are crucial regulators of synaptic plasticity, fine-tuning the function of this key protein depending on the specific situation. The extensive cross-talk between signalling pathways and the numerous routes of Arc regulation provide a complex interplay of processes in which Arc-mediated plasticity can be broadly induced, but specifically tailored to synaptic activity. Here we provide an overview what is currently known about these processes and potential future directions.
Abstract.
Carmichael RE, Boyce A, Matthewman C, Patron NJ (2015). An introduction to synthetic biology in plant systems: ERASynBio/OpenPlant summer school for early career researchers, September 2014. New Phytologist, 208(1), 20-22.
Luo J, Ashikaga E, Rubin PP, Heimann MJ, Hildick KL, Bishop P, Girach F, Josa-Prado F, Tang LTH, Carmichael RE, et al (2013). Receptor trafficking and the regulation of synaptic plasticity by SUMO.
NeuroMolecular Medicine,
15(4), 692-706.
Abstract:
Receptor trafficking and the regulation of synaptic plasticity by SUMO
Timely and efficient information transfer at synapses is fundamental to brain function. Synapses are highly dynamic structures that exhibit long-lasting activity-dependent alterations to their structure and transmission efficiency, a phenomenon termed synaptic plasticity. These changes, which occur through alterations in presynaptic release or in the trafficking of postsynaptic receptor proteins, underpin the formation and stabilisation of neural circuits during brain development, and encode, process and store information essential for learning, memory and cognition. In recent years, it has emerged that the ubiquitin-like posttranslational modification SUMOylation is an important mediator of several aspects of neuronal and synaptic function. Through orchestrating synapse formation, presynaptic release and the trafficking of postsynaptic receptor proteins during forms of synaptic plasticity such as long-term potentiation, long-term depression and homeostatic scaling, SUMOylation is being increasingly appreciated to play a central role in neurotransmission. In this review, we outline key discoveries in this relatively new field, provide an update on recent progress regarding the targets and consequences of protein SUMOylation in synaptic function and plasticity, and highlight key outstanding questions regarding the roles of protein SUMOylation in the brain. © 2013 Springer Science+Business Media New York.
Abstract.
Chapters
Schrader M (2023). Immunolabelling for detection of endogenous and overexpressed peroxisomal proteins in mammalian cells. In (Ed) , Springer.
Wilkinson KA, McMillan KJ, Banks PJ, Carmichael RE, Nakamura Y, Bashir ZI, Cullen PJ, Henley JM (2022). Using Lentiviral shRNA Delivery to Knock Down Proteins in Cultured Neurons and in Vivo. In (Ed) Translational Research Methods in Neurodevelopmental Disorders, Springer Nature, 1-17.
Publications by year
In Press
Azadi AS, Carmichael RE, Kovacs WJ, Koster J, Kors S, Waterham HR, Schrader M (In Press). A functional SMAD2/3 binding site in the PEX11β promoter identifies a role for TGFβ in peroxisome proliferation in humans. Frontiers in Cell and Developmental Biology
Schrader M, Carmichael R (In Press). Determinants of peroxisome membrane dynamics. Frontiers in Physiology
Carmichael RE, Islinger M, Schrader M (In Press). Fission Impossible (?) – New Insights into Disorders of Peroxisome Dynamics. Cells
Soares Carneiro Da Silva B, DiGiovanni L, Kumar R, Carmichael RE, Kim PK, Schrader M (In Press). Maintaining social contacts: the physiological relevance of organelle interactions. BBA: Molecular Cell Research
Passmore J, Carmichael R, Schrader T, Godinho L, Ferdinandusse S, Lismont C, Wang Y, Hacker C, Islinger M, Fransen M, et al (In Press). Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation. BBA: Molecular Cell Research
Carmichael R, Richards D, Fahimi HD, Schrader M (In Press). Organelle Membrane Extensions in Mammalian Cells. Biology
Schrader T, Carmichael R, Islinger M, Costello J, Hacker C, Bonekamp N, Weishaupt J, Andersen P, Schrader M (In Press). PEX11β and FIS1 cooperate in peroxisome division independent of Mitochondrial Fission Factor. Journal of Cell Science
2023
Silva B, Schrader TA, Schrader M, Carmichael R (2023). Generation of reporter cell lines for endogenous expression analysis of peroxisomal proteins. Methods in Molecular Biology
Schrader T, Carmichael R, Schrader M (2023). Immunolabelling for detection of endogenous and overexpressed peroxisomal proteins in mammalian cells. Methods in Molecular Biology
Schrader TA, Carmichael R, Schrader M (2023). Immunolabelling for detection of endogenous and overexpressed peroxisomal proteins in mammalian cells., Springer.
Schrader M (2023). Immunolabelling for detection of endogenous and overexpressed peroxisomal proteins in mammalian cells. In (Ed) , Springer.
2022
Soares ES, de Souza ACG, Zanella CA, Carmichael RE, Henley JM, Wilkinson KA, Cimarosti HI (2022). Effects of amyloid-β on protein SUMOylation and levels of mitochondrial proteins in primary cortical neurons. IBRO Neuroscience Reports, 12, 142-148.
Angelika T, Carmichael R (2022). First person - Tina Angelika Schrader and Ruth Carmichael.
JOURNAL OF CELL SCIENCE,
135(13).
Author URL.
Waters E, Wilkinson KA, Harding AL, Carmichael RE, Robinson D, Colley HE, Guo C (2022). The SUMO protease SENP3 regulates mitochondrial autophagy mediated by Fis1.
EMBO REPORTS,
23(2).
Author URL.
Wilkinson KA, McMillan KJ, Banks PJ, Carmichael RE, Nakamura Y, Bashir ZI, Cullen PJ, Henley JM (2022). Using Lentiviral shRNA Delivery to Knock Down Proteins in Cultured Neurons and in Vivo. In (Ed) Translational Research Methods in Neurodevelopmental Disorders, Springer Nature, 1-17.
2021
McMillan KJ, Banks PJ, Hellel FLN, Carmichael RE, Clairfeuille T, Evans AJ, Heesom KJ, Lewis P, Collins BM, Bashir ZI, et al (2021). Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2.
eLife,
10Abstract:
Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2
The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through sorting of integral proteins to the synaptic surface, most notably AMPA receptors. To provide a broader view of SNX27-associated pathologies, we performed proteomics in rat primary neurons to identify SNX27-dependent cargoes, and identified proteins linked to excitotoxicity, epilepsy, intellectual disabilities, and working memory deficits. Focusing on the synaptic adhesion molecule LRFN2, we established that SNX27 binds to LRFN2 and regulates its endosomal sorting. Furthermore, LRFN2 associates with AMPA receptors and knockdown of LRFN2 results in decreased surface AMPA receptor expression, reduced synaptic activity, and attenuated hippocampal long-term potentiation. Overall, our study provides an additional mechanism by which SNX27 can control AMPA receptor-mediated synaptic transmission and plasticity indirectly through the sorting of LRFN2 and offers molecular insight into the perturbed function of SNX27 and LRFN2 in a range of neurological conditions.
Abstract.
2020
Passmore JB, Godinho LF, Ferdinandusse S, Lismont C, Wang Y, Hacker C, Islinger M, Fransen M, Richards DM, Freisinger P, et al (2020). Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation.
bioRxiv, 2020.01.08.898486-2020.01.08.898486.
Abstract:
Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation
Peroxisomes are highly dynamic subcellular compartments with important functions in lipid and ROS metabolism. Impaired peroxisomal function can lead to severe metabolic disorders with developmental defects and neurological abnormalities. Recently, a new group of disorders has been identified, characterised by defects in the membrane dynamics and division of peroxisomes rather than by loss of metabolic functions. However, the contribution of impaired peroxisome plasticity to the pathophysiology of those disorders is not well understood. Mitochondrial fission factor (MFF) is a key component of both the peroxisomal and mitochondrial division machinery. Patients with MFF deficiency present with developmental and neurological abnormalities. Peroxisomes (and mitochondria) in patient fibroblasts are highly elongated as a result of impaired organelle division. The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown. Here, we show that MFF deficiency does not cause alterations to overall peroxisomal biochemical function. However, loss of MFF results in reduced import-competency of the peroxisomal compartment and leads to the accumulation of pre-peroxisomal membrane structures. We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH as well as altered distribution in neuronal cells. Removal of elongated peroxisomes through induction of autophagic processes is not impaired. A mathematical model describing key processes involved in peroxisome dynamics sheds further light into the physical processes disturbed in MFF-deficient cells. The consequences of our findings for the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity are discussed. ACOX1 :. acyl-CoA oxidase 1; PBD :. peroxisome biogenesis disorder; PED :. single peroxisomal enzyme deficiency; DRP1 :. dynamin-related protein 1; ER :. endoplasmic reticulum; FIS1 :. mitochondrial fission 1 protein; MFF :. Mitochondrial fission factor; ROS :. reactive oxygen species; PTS :. peroxisome targeting signal; VLCFA :. very-long-chain fatty acid.
Abstract.
McMillan KJ, Banks PJ, Hellel FLN, Carmichael RE, Clairfeuille T, Evans AJ, Heesom KJ, Lewis P, Collins BM, Bashir ZI, et al (2020). Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2.
2019
Carmichael RE, Wilkinson KA, Craig TJ (2019). Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes.
Scientific Reports,
9(1).
Abstract:
Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes
Type-II Diabetes Mellitus (T2DM) is one of the fastest growing public health issues today, consuming 12% of worldwide health budgets and affecting an estimated 400 million people. One of the key pathological traits of this disease is insulin resistance at ‘glucose sink’ tissues (mostly skeletal muscle), and this remains one of the features of this disease most intractable to therapeutic intervention. Several lines of evidence have implicated the post-translational modification, SUMOylation, in insulin signalling and insulin resistance in skeletal muscle. In this study, we examined this possibility by manipulation of cellular SUMOylation levels using multiple different tools, and assaying the effect on insulin-stimulated GLUT4 surface expression in differentiated L6 rat myocytes. Although insulin stimulation of L6 myocytes produced a robust decrease in total cellular SUMO1-ylation levels, manipulating cellular SUMOylation had no effect on insulin-responsive GLUT4 surface trafficking using any of the tools we employed. Whilst we cannot totally exclude the possibility that SUMOylation plays a role in the insulin signalling pathway in human health and disease, our data strongly argue that GLUT4 trafficking in response to insulin is not regulated by protein SUMOylation, and that SUMOylation does not therefore represent a viable therapeutic target for the treatment of insulin resistance.
Abstract.
Davey JS, Carmichael RE, Craig TJ (2019). Protein SUMOylation regulates insulin secretion at multiple stages.
Scientific Reports,
9(1).
Abstract:
Protein SUMOylation regulates insulin secretion at multiple stages
Type-II Diabetes Mellitus (T2DM) is one of the fastest growing public health issues of modern times, consuming 12% of worldwide health budgets and affecting an estimated 400 million people. A key pathological trait associated with this disease is the failure of normal glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells. Several lines of evidence suggest that vesicle trafficking events such as insulin secretion are regulated by the post-translational modification, SUMOylation, and indeed SUMOylation has been proposed to act as a ‘brake’ on insulin exocytosis. Here, we show that diabetic stimuli which inhibit GSIS are correlated with an increase in cellular protein SUMOylation, and that inhibition of deSUMOylation reduces GSIS. We demonstrate that manipulation of cellular protein SUMOylation levels, by overexpression of several different components of the SUMOylation pathway, have varied and complex effects on GSIS, indicating that SUMOylation regulates this process at multiple stages. We further demonstrate that inhibition of syntaxin1A SUMOylation, via a knockdown-rescue strategy, greatly enhances GSIS. Our data are therefore consistent with the model that SUMOylation acts as a brake on GSIS, and we have identified SUMOylation of syntaxin 1 a as a potential component of this brake. However, our data also demonstrate that the role of SUMOylation in GSIS is complex and may involve many substrates.
Abstract.
Waters E, Wilkinson KA, Carmichael RE, Guo C (2019). The SUMO Protease SENP3 regulates Mitochondrial Autophagy mediated by Fis1.
2018
Henley JM, Carmichael RE, Wilkinson KA (2018). Extranuclear SUMOylation in Neurons.
Trends in Neurosciences,
41(4), 198-210.
Abstract:
Extranuclear SUMOylation in Neurons
Post-translational modification of substrate proteins by SUMO conjugation regulates a diverse array of cellular processes. While predominantly a nuclear protein modification, there is a growing appreciation that SUMOylation of proteins outside the nucleus plays direct roles in controlling synaptic transmission, neuronal excitability, and adaptive responses to cell stress. Furthermore, alterations in protein SUMOylation are observed in a wide range of neurological and neurodegenerative diseases, and several extranuclear disease-associated proteins have been shown to be directly SUMOylated. Here, focusing mainly on SUMOylation of synaptic and mitochondrial proteins, we outline recent developments and discoveries, and present our opinion as to the most exciting avenues for future research to define how SUMOylation of extranuclear proteins regulates neuronal and synaptic function.
Abstract.
Carmichael RE, Wilkinson KA, Craig TJ, Ashby MC, Henley JM (2018). MEF2A regulates mGluR-dependent AMPA receptor trafficking independently of Arc/Arg3.1.
SCIENTIFIC REPORTS,
8 Author URL.
Zhu B, Carmichael RE, Valois LS, Wilkinson KA, Henley JM (2018). The transcription factor MEF2A plays a key role in the differentiation/ maturation of rat neural stem cells into neurons.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,
500(3), 645-649.
Author URL.
Carmichael RE, Henley JM (2018). Transcriptional and post-translational regulation of Arc in synaptic plasticity.
Seminars in Cell and Developmental Biology,
77, 3-9.
Abstract:
Transcriptional and post-translational regulation of Arc in synaptic plasticity
One of the most interesting features of Arc-dependent synaptic plasticity is how multiple types of synaptic activity can converge to alter Arc transcription and then diverge to induce different plasticity outcomes, ranging from AMPA receptor internalisation that promotes long-term depression (LTD), to actin stabilisation that promotes long-term potentiation (LTP). This diversity suggests that there must be numerous levels of control to ensure the temporal profile, abundance, localisation and function of Arc are appropriately regulated to effect learning and memory in the correct contexts. The activity-dependent transcription and post-translational modification of Arc are crucial regulators of synaptic plasticity, fine-tuning the function of this key protein depending on the specific situation. The extensive cross-talk between signalling pathways and the numerous routes of Arc regulation provide a complex interplay of processes in which Arc-mediated plasticity can be broadly induced, but specifically tailored to synaptic activity. Here we provide an overview what is currently known about these processes and potential future directions.
Abstract.
2015
Carmichael RE, Boyce A, Matthewman C, Patron NJ (2015). An introduction to synthetic biology in plant systems: ERASynBio/OpenPlant summer school for early career researchers, September 2014. New Phytologist, 208(1), 20-22.
2013
Luo J, Ashikaga E, Rubin PP, Heimann MJ, Hildick KL, Bishop P, Girach F, Josa-Prado F, Tang LTH, Carmichael RE, et al (2013). Receptor trafficking and the regulation of synaptic plasticity by SUMO.
NeuroMolecular Medicine,
15(4), 692-706.
Abstract:
Receptor trafficking and the regulation of synaptic plasticity by SUMO
Timely and efficient information transfer at synapses is fundamental to brain function. Synapses are highly dynamic structures that exhibit long-lasting activity-dependent alterations to their structure and transmission efficiency, a phenomenon termed synaptic plasticity. These changes, which occur through alterations in presynaptic release or in the trafficking of postsynaptic receptor proteins, underpin the formation and stabilisation of neural circuits during brain development, and encode, process and store information essential for learning, memory and cognition. In recent years, it has emerged that the ubiquitin-like posttranslational modification SUMOylation is an important mediator of several aspects of neuronal and synaptic function. Through orchestrating synapse formation, presynaptic release and the trafficking of postsynaptic receptor proteins during forms of synaptic plasticity such as long-term potentiation, long-term depression and homeostatic scaling, SUMOylation is being increasingly appreciated to play a central role in neurotransmission. In this review, we outline key discoveries in this relatively new field, provide an update on recent progress regarding the targets and consequences of protein SUMOylation in synaptic function and plasticity, and highlight key outstanding questions regarding the roles of protein SUMOylation in the brain. © 2013 Springer Science+Business Media New York.
Abstract.