Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission Journal Article
| Authors: | Christophers, B.; Leahy, S. N.; Soffar, D. B.; von Saucken, V. E.; Broadie, K.; Baylies, M. K. |
| Article Title: | Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission |
| 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. © 2024. Published by The Company of Biologists Ltd. |
| Keywords: | genetics; nonhuman; animal; metabolism; animals; actin; gene expression; pathology; growth, development and aging; drosophila melanogaster; actins; glutamate receptor; drosophila proteins; gene knockdown techniques; drosophila protein; muscle; muscle development; synaptic transmission; neuromuscular junction; actin filament; cofilin; actin cytoskeleton; sarcomere; actin depolymerizing factor; gene knockdown; article; rna sequencing; nemaline myopathy; myopathies, nemaline; sarcomeres; cofilin (cfl); postsynapse; twinstar (tsr); actin depolymerizing factors |
| Journal Title: | Development |
| Volume: | 151 |
| Issue: | 13 |
| ISSN: | 0950-1991 |
| Publisher: | Company of Biologists |
| Date Published: | 2024-07-01 |
| Start Page: | dev202558 |
| Language: | English |
| DOI: | 10.1242/dev.202558 |
| PUBMED: | 38869008 |
| PROVIDER: | scopus |
| PMCID: | PMC11266751 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Mary K. Baylies -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work