RRC ID 81496
Author Christophers B, Leahy SN, Soffar DB, von Saucken VE, Broadie K, Baylies MK.
Title Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission.
Journal Development
Abstract Cofilin, an actin-severing protein, plays key roles in muscle sarcomere addition and maintenance. Our previous work found that Drosophila cofilin (DmCFL) knockdown in muscle causes progressive deterioration of muscle structure and function and produces features seen in nemaline myopathy caused by cofilin mutations. We hypothesized that disruption of actin cytoskeleton dynamics by DmCFL knockdown would impact other aspects of muscle development, and, thus, conducted an RNA-sequencing analysis that unexpectedly revealed upregulated expression of numerous neuromuscular junction (NMJ) genes. We found that DmCFL is enriched in the muscle postsynaptic compartment and that DmCFL muscle knockdown causes F-actin disorganization in this subcellular domain prior to the sarcomere defects observed later in development. Despite NMJ gene expression changes, we found no significant changes in gross presynaptic Bruchpilot active zones or total postsynaptic glutamate receptor levels. However, DmCFL knockdown resulted in mislocalization of GluRIIA class glutamate receptors in more deteriorated muscles and strongly impaired NMJ transmission strength. These findings expand our understanding of the roles of cofilin in muscle to include NMJ structural development and suggest that NMJ defects may contribute to the pathophysiology of nemaline myopathy.
Volume 151(13)
Published 2024-7-1
DOI 10.1242/dev.202558
PII 353091
PMID 38869008
PMC PMC11266751
MeSH Actin Cytoskeleton / metabolism Actin Depolymerizing Factors / genetics Actin Depolymerizing Factors / metabolism Actins / metabolism Animals Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster* / genetics Drosophila melanogaster* / growth & development Drosophila melanogaster* / metabolism Gene Knockdown Techniques Myopathies, Nemaline / genetics Myopathies, Nemaline / metabolism Myopathies, Nemaline / pathology Neuromuscular Junction* / metabolism Sarcomeres / metabolism Synaptic Transmission*
IF 5.611
Resource
Drosophila