An UNC-40 pathway directs postsynaptic membrane extension in Caenorhabditis elegans.
The postsynaptic membrane of the embryonic neuromuscular junction undergoes a dramatic expansion during later development to facilitate the depolarization of larger muscles. In C. elegans, the postsynaptic membrane resides at the termini of plasma membrane extensions called muscle arms. Membrane extension to the motor axons during larval development doubles the number of muscle arms, making them a tractable model to investigate both postsynaptic membrane expansion and guided membrane extension. To identify genes required for muscle arm extension, we performed a forward screen for mutants with fewer muscle arms. We isolated 23 mutations in 14 genes, including unc-40/Dcc, which encodes a transmembrane receptor that guides the migration of cells and extending axons in response to the secreted UNC-6/Netrin spatial cue. We discovered that UNC-40 is enriched at muscle arm termini and functions cell-autonomously to direct arm extension to the motor axons. Surprisingly, UNC-6 is dispensable for muscle arm extension, suggesting that UNC-40 relies on other spatial cues to direct arm extension. We provide the first evidence that the guanine-nucleotide exchange factor UNC-73/Trio, members of the WAVE actin-polymerization complex, and a homolog of the focal adhesion complex can function downstream of UNC-40 to direct membrane extension. Our work is the first to define a pathway for directed muscle membrane extension and illustrates that axon guidance components can play key roles in postsynaptic membrane expansion.
Alexander
Mariam
M
Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, 160 College Street, University of Toronto, Toronto, ON, M5S 3E1, Canada.
Chan
Kevin Ka Ming
KK
Byrne
Alexandra B
AB
Selman
Guillermo
G
Lee
Teresa
T
Ono
Jasmine
J
Wong
Eric
E
Puckrin
Rachel
R
Dixon
Scott J
SJ
Roy
Peter John
PJ
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D009132:Muscles / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000075385:Netrins; D013569:Synapses / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins; D000075385:Netrins; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans; C111263:UNC-73 protein, C elegans