| RRC ID |
46105
|
| Author |
Han SM, Tsuda H, Yang Y, Vibbert J, Cottee P, Lee SJ, Winek J, Haueter C, Bellen HJ, Miller MA.
|
| Title |
Secreted VAPB/ALS8 major sperm protein domains modulate mitochondrial localization and morphology via growth cone guidance receptors.
|
| Journal |
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.
|
| Volume |
22(2)
|
| Pages |
348-62
|
| Published |
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
|
| Times Cited |
44
|
|
WOS Category
|
DEVELOPMENTAL BIOLOGY
CELL BIOLOGY
|
| Resource |
| C.elegans |
tm1411
tm1441 |
