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 Full text.
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 Full text.
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.
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.