Title | Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Christophers B, Leahy SN, Soffar DB, von Saucken VE, Broadie K, Baylies MK |
Journal | Development |
Volume | 151 |
Issue | 13 |
Date Published | 2024 Jul 01 |
ISSN | 1477-9129 |
Keywords | Actin Cytoskeleton, Actin Depolymerizing Factors, Actins, Animals, Drosophila melanogaster, Drosophila Proteins, Gene Knockdown Techniques, Myopathies, Nemaline, Neuromuscular Junction, Sarcomeres, Synaptic Transmission |
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. |
DOI | 10.1242/dev.202558 |
Alternate Journal | Development |
PubMed ID | 38869008 |
Grant List | F30HD111309-01 / NH / NIH HHS / United States P30 CA 008748 / CA / NCI NIH HHS / United States F30HD111309-01 / NH / NIH HHS / United States |
Submitted by bel2021 on July 15, 2024 - 11:49am