The secreted MSP domain of C. elegans VAPB homolog VPR-1 patterns the adult striated muscle mitochondrial reticulum via SMN-1

Jessica Schultz, Se Jin Lee, Tim Cole, Hieu D. Hoang, Jack Vibbert, Pauline A. Cottee, Michael A. Miller, Sung Min Han

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2175-2186
Number of pages12
JournalJournal of Cell Science
Volume130
Issue number13
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

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Keywords

  • ALS
  • Amyotrophic lateral sclerosis
  • Major sperm protein domain
  • Mitochondria
  • MSP
  • SMA
  • SMN-1
  • Spinal muscular atrophy
  • Striated muscle
  • VAPA
  • VAPB

ASJC Scopus subject areas

  • Cell Biology

Cite this

Schultz, J., Lee, S. J., Cole, T., Hoang, H. D., Vibbert, J., Cottee, P. A., Miller, M. A., & Han, S. M. (2017). The secreted MSP domain of C. elegans VAPB homolog VPR-1 patterns the adult striated muscle mitochondrial reticulum via SMN-1. Journal of Cell Science, 130(13), 2175-2186. https://doi.org/10.1242/dev.152025