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Title: The CHD Protein, Kismet, is Important for the Recycling of Synaptic Vesicles during Endocytosis
Abstract

Chromatin remodeling proteins of the chromodomain DNA-binding protein family, CHD7 and CHD8, mediate early neurodevelopmental events including neural migration and differentiation. As such, mutations in either protein can lead to neurodevelopmental disorders. How chromatin remodeling proteins influence the activity of mature synapses, however, is relatively unexplored. A critical feature of mature neurons is well-regulated endocytosis, which is vital for synaptic function to recycle membrane and synaptic proteins enabling the continued release of synaptic vesicles. Here we show that Kismet, theDrosophilahomolog of CHD7 and CHD8, regulates endocytosis. Kismet positively influenced transcript levels and bound todap160andendophilin Btranscription start sites and promoters in whole nervous systems and influenced the synaptic localization of Dynamin/Shibire. In addition,kismetmutants exhibit reduced VGLUT, a synaptic vesicle marker, at stimulated but not resting synapses and reduced levels of synaptic Rab11. Endocytosis is restored atkismetmutant synapses by pharmacologically inhibiting the function of histone deacetyltransferases (HDACs). These data suggest that HDAC activity may oppose Kismet to promote synaptic vesicle endocytosis. A deeper understanding of how CHD proteins regulate the function of mature neurons will help better understand neurodevelopmental disorders.

Authors:
; ; ; ; ; ; ;
Award ID(s):
1856439
Publication Date:
NSF-PAR ID:
10153807
Journal Name:
Scientific Reports
Volume:
9
Issue:
1
ISSN:
2045-2322
Publisher:
Nature Publishing Group
Sponsoring Org:
National Science Foundation
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