RRC ID 51417
著者 Schultz J, Lee SJ, Cole T, Hoang HD, Vibbert J, Cottee PA, Miller MA, Han SM.
タイトル The secreted MSP domain of C. elegans VAPB homolog VPR-1 patterns the adult striated muscle mitochondrial reticulum via SMN-1.
ジャーナル Development
Abstract The major sperm protein domain (MSPd) has an extracellular signaling function implicated in amyotrophic lateral sclerosis. Secreted MSPds derived from the C. elegans VAPB homolog VPR-1 promote mitochondrial localization to actin-rich I-bands in body wall muscle. Here we show that the nervous system and germ line are key MSPd secretion tissues. MSPd signals are transduced through the CLR-1 Lar-like tyrosine phosphatase receptor. We show that CLR-1 is expressed throughout the muscle plasma membrane, where it is accessible to MSPd within the pseudocoelomic fluid. MSPd signaling is sufficient to remodel the muscle mitochondrial reticulum during adulthood. An RNAi suppressor screen identified survival of motor neuron 1 (SMN-1) as a downstream effector. SMN-1 acts in muscle, where it colocalizes at myofilaments with ARX-2, a component of the Arp2/3 actin-nucleation complex. Genetic studies suggest that SMN-1 promotes Arp2/3 activity important for localizing mitochondria to I-bands. Our results support the model that VAPB homologs are circulating hormones that pattern the striated muscle mitochondrial reticulum. This function is crucial in adults and requires SMN-1 in muscle, likely independent of its role in pre-mRNA splicing.
巻・号 144(12)
ページ 2175-2186
公開日 2017-6-15
DOI 10.1242/dev.152025
PII 144/12/2175
PMID 28634272
PMC PMC5482996
MeSH Actin-Related Protein 2 / metabolism Actin-Related Protein 2-3 Complex / metabolism Amyotrophic Lateral Sclerosis / metabolism Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Genes, Helminth Germ Cells / metabolism Humans Larva / growth & development Larva / metabolism Male Membrane Proteins / chemistry Membrane Proteins / genetics Membrane Proteins / metabolism* Mitochondria, Muscle / metabolism Motor Neurons / metabolism Muscle, Striated / growth & development* Muscle, Striated / metabolism* Mutation Protein Domains RNA Interference Receptor-Like Protein Tyrosine Phosphatases / genetics Receptor-Like Protein Tyrosine Phosphatases / metabolism SMN Complex Proteins / antagonists & inhibitors SMN Complex Proteins / genetics SMN Complex Proteins / metabolism* Sarcolemma / metabolism Signal Transduction
IF 5.611
引用数 3
リソース情報
線虫 tm1411 tm1441