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Emerging mechanisms and consequences of calcium regulation of alternative splicing in neurons and endocrine cells

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Abstract

Alternative splicing contributes greatly to proteomic complexity. How it is regulated by external stimuli to sculpt cellular properties, particularly the highly diverse and malleable neuronal properties, is an underdeveloped area of emerging interest. A number of recent studies in neurons and endocrine cells have begun to shed light on its regulation by calcium signals. Some mechanisms include changes in the trans-acting splicing factors by phosphorylation, protein level, alternative pre-mRNA splicing, and nucleocytoplasmic redistribution of proteins to alter protein–RNA or protein–protein interactions, as well as modulation of chromatin states. Importantly, functional analyses of the control of specific exons/splicing factors in the brain point to a crucial role of this regulation in synaptic maturation, maintenance, and transmission. Furthermore, its deregulation has been implicated in the pathogenesis of neurological disorders, particularly epilepsy/seizure. Together, these studies have not only provided mechanistic insights into the regulation of alternative splicing by calcium signaling but also demonstrated its impact on neuron differentiation, function, and disease. This may also help our understanding of similar regulations in other types of cells.

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Acknowledgments

We thank Drs. Ruey-Chyi Su, Guodong Liu (University of Manitoba) and Ingo Greger (MRC, Cambridge) for helpful comments. This work was supported by the Canadian Institutes of Health Research FRN_106608 to J.X.

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Authors and Affiliations

  1. Department of Physiology, University of Manitoba, 439 BMSB, 745 Bannatyne Ave, Winnipeg, R3E 0J9, Canada

    Aleh Razanau & Jiuyong Xie

  2. Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada

    Jiuyong Xie

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  1. Aleh Razanau
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  2. Jiuyong Xie
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Correspondence to Jiuyong Xie.

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Razanau, A., Xie, J. Emerging mechanisms and consequences of calcium regulation of alternative splicing in neurons and endocrine cells. Cell. Mol. Life Sci. 70, 4527–4536 (2013). https://doi.org/10.1007/s00018-013-1390-5

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  • DOI: https://doi.org/10.1007/s00018-013-1390-5

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