Title | Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Christophers B, Leahy SN, Soffar DB, von Saucken VE, Broadie K, Baylies MK |
Journal | bioRxiv |
Date Published | 2023 Nov 22 |
Abstract | Cofilin, an actin severing protein, plays critical roles in muscle sarcomere addition and maintenance. Our previous work has shown Drosophila cofilin (DmCFL) knockdown causes progressive deterioration of muscle structure and function and produces features seen in nemaline myopathy (NM) 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 which unexpectedly revealed upregulated expression of numerous neuromuscular junction (NMJ) genes. We found that DmCFL is enriched in the muscle postsynaptic compartment and that DmCFL deficiency 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 results in mislocalization of glutamate receptors containing the GluRIIA subunit in more deteriorated muscles and neurotransmission strength is strongly impaired. These findings expand our understanding of cofilin's roles in muscle to include NMJ structural development and suggest that NMJ defects may contribute to NM pathophysiology. |
DOI | 10.1101/2023.11.21.568166 |
Alternate Journal | bioRxiv |
PubMed ID | 38045306 |
PubMed Central ID | PMC10690168 |
Grant List | F30 HD111309 / HD / NICHD NIH HHS / United States R01 AR068128 / AR / NIAMS NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States T32 HD060600 / HD / NICHD NIH HHS / United States R01 MH084989 / MH / NIMH NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
Submitted by bel2021 on February 16, 2024 - 10:44am