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Lookup NU author(s): Dr Ingrid Ehrmann, Caroline Dalgliesh, Dr Yaobo Xu, Dr Marina Danilenko, Marie Maclennan, Dr Gavin ClowryORCiD, Professor Mark Cunningham, Professor David Elliott
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The brain is made up of trillions of synaptic connections that together form neural networks needed fornormal brain function and behavior. SLM2 is a member of a conserved family of RNA binding proteins,including Sam68 and SLM1, that control splicing of Neurexin1-3 pre-mRNAs. Whether SLM2 affects neuralnetwork activity is unknown. Here, we find thatSLM2 levels are maintained by a homeostatic feedbackcontrol pathway that predates the divergenceof SLM2 and Sam68. SLM2 also controls the splicingof Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, andCask, each of which are important for synapse function.Cortical neural network activity dependent onsynaptic connections between SLM2-expressingpyramidalneurons and interneurons is decreased inSlm2-null mice. Additionally, these mice are anxiousand have a decreased ability to recognize novelobjects. Our data reveal a pathway of SLM2 homeostaticauto-regulation controlling brain network activityand behaviour.
Author(s): Ehrmann I, Gazzara MR, Pagliarini V, Dalgliesh C, Kheirollahi-Chadegani M, Xu Y, Cesari E, Danilenko M, Maclennan M, Lowdon K, Vogel T, Keskivali-Bond P, Wells S, Cater H, Fort P, Sanibanez-Koref M, Middei S, Sette C, Clowry GJ, Barash Y, Cunningham MO, Elliott DJ
Publication type: Article
Publication status: Published
Journal: Cell Reports
Year: 2016
Volume: 17
Issue: 12
Pages: 3269-3280
Online publication date: 20/12/2016
Acceptance date: 29/11/2016
Date deposited: 19/01/2017
ISSN (electronic): 2211-1247
Publisher: Elsevier Inc
URL: http://dx.doi.org/10.1016/j.celrep.2016.12.002
DOI: 10.1016/j.celrep.2016.12.002
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