Dscam2 suppresses synaptic strength through a PI3K-dependent endosomal pathway.

Autor:	Odierna GL; School of Biomedical Sciences, The University of Queensland, Brisbane, Australia., Kerwin SK; School of Biomedical Sciences, The University of Queensland, Brisbane, Australia., Harris LE; School of Biomedical Sciences, The University of Queensland, Brisbane, Australia., Shin GJ; School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY., Lavidis NA; School of Biomedical Sciences, The University of Queensland, Brisbane, Australia., Noakes PG; School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.; Queensland Brain Institute, The University of Queensland, Brisbane, Australia., Millard SS; School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2020 Jun 01; Vol. 219 (6).
DOI:	10.1083/jcb.201909143
Abstrakt:	Dscam2 is a cell surface protein required for neuronal development in Drosophila; it can promote neural wiring through homophilic recognition that leads to either adhesion or repulsion between neurites. Here, we report that Dscam2 also plays a post-developmental role in suppressing synaptic strength. This function is dependent on one of two distinct extracellular isoforms of the protein and is autonomous to motor neurons. We link the PI3K enhancer, Centaurin gamma 1A, to the Dscam2-dependent regulation of synaptic strength and show that changes in phosphoinositide levels correlate with changes in endosomal compartments that have previously been associated with synaptic strength. Using transmission electron microscopy, we find an increase in synaptic vesicles at Dscam2 mutant active zones, providing a rationale for the increase in synaptic strength. Our study provides the first evidence that Dscam2 can regulate synaptic physiology and highlights how diverse roles of alternative protein isoforms can contribute to unique aspects of brain development and function. (© 2020 Odierna et al.)
Databáze:	MEDLINE
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