UNC-1 regulates gap junctions important to locomotion in C. elegans.
In C. elegans, loss-of-function (lf) mutations of the stomatin-like protein (SLP) UNC-1 and the innexin UNC-9 inhibit locomotion [1, 2] and modulate sensitivity to volatile anesthetics [3, 4]. It was unknown why unc-1(lf) and unc-9(lf) mutants have similar phenotypes. We tested the hypothesis that UNC-1 is a regulator of gap junctions formed by UNC-9. Analyses of junctional currents between body-wall muscle cells showed that electrical coupling was inhibited to a similar degree in unc-1(lf), unc-9(lf), and unc-1(lf);unc-9(lf) double mutants, suggesting that UNC-1 and UNC-9 function together. Expression of Punc-1::DsRED2 and Punc-9::GFP transcriptional fusions suggests that unc-1 and unc-9 are coexpressed in neurons and body-wall muscle cells. Immunohistochemistry showed that UNC-1 and UNC-9 colocalized at intercellular junctions and that unc-1(lf) did not alter UNC-9 expression or subcellular localization. Bimolecular fluorescence complementation (BiFC) assays suggest that UNC-1 and UNC-9 are physically very close at intercellular junctions. Targeted rescue experiments suggest that UNC-9 and UNC-1 function predominantly in neurons to control locomotion. Thus, in addition to the recently reported function of regulating mechanosensitive ion channels [5, 6], SLPs might have a novel function of regulating gap junctions.
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06030.
Bojun
B
Chen
Qiang
Q
Liu
Qian
Q
Ge
Jia
J
Xie
Zhao-Wen
ZW
Wang
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D017629:Gap Junctions / Q000378:metabolism*; D008124:Locomotion / Q000502:physiology; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000502:physiology; D009474:Neurons / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C113701:Unc-1 protein, C elegans; C109201:Unc-9 protein, C elegans