RRC ID 46105
著者 Han SM, Tsuda H, Yang Y, Vibbert J, Cottee P, Lee SJ, Winek J, Haueter C, Bellen HJ, Miller MA.
タイトル Secreted VAPB/ALS8 major sperm protein domains modulate mitochondrial localization and morphology via growth cone guidance receptors.
ジャーナル Dev Cell
Abstract VIDEO ABSTRACT:The VAPB/ALS8 major sperm protein domain (vMSP) is implicated in amyotrophic lateral sclerosis and spinal muscular atrophy, yet its function in the nervous system is not well understood. In Caenorhabditis elegans and Drosophila, the vMSP is cleaved from its transmembrane anchor and secreted in a cell type-specific fashion. We show that vMSPs secreted by neurons act on Lar-like protein-tyrosine phosphatase and Roundabout growth cone guidance receptors expressed in striated muscle. This signaling pathway promotes Arp2/3-dependent actin remodeling and mitochondrial localization to actin-rich muscle I-bands. C. elegans VAPB mutants have mitochondrial localization, morphology, mobility, and fission/fusion defects that are suppressed by Lar-like receptor or Arp2/3 inactivation. Hence, growth cone guidance receptor pathways that remodel the actin cytoskeleton have unanticipated effects on mitochondrial dynamics. We propose that neurons secrete vMSPs to promote striated muscle energy production and metabolism, in part through the regulation of mitochondrial localization and function.
巻・号 22(2)
ページ 348-62
公開日 2012-2-14
DOI 10.1016/j.devcel.2011.12.009
PII S1534-5807(11)00575-2
PMID 22264801
PMC PMC3298687
MeSH Actin-Related Protein 2-3 Complex / metabolism Actins / metabolism Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Fluorescence Growth Cones / metabolism* Helminth Proteins / genetics Helminth Proteins / metabolism* Mitochondria / metabolism* Mitochondria / pathology Muscle, Striated / cytology Muscle, Striated / metabolism* Neurons / cytology Neurons / metabolism* Protein Structure, Tertiary Signal Transduction Transgenes / physiology
IF 10.092
引用数 44
WOS 分野 DEVELOPMENTAL BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm1411 tm1441