Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans

被引:263
作者
Liedtke, W
Tobin, DM
Bargmann, CI [1 ]
Friedman, JM
机构
[1] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Biochem & Biophys, Program Dev Biol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Genet Program, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Program Neurosci, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
[6] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
[7] Rockefeller Univ, Mol Genet Lab, New York, NY 10021 USA
关键词
D O I
10.1073/pnas.2235619100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
All animals detect osmotic and mechanical stimuli, but the molecular basis for these responses is incompletely understood. The vertebrate transient receptor potential channel vanilloid subfamily 4 (TRPV4) (VR-OAC) cation channel has been suggested to be an osmo/mechanosensory channel. To assess its function in vivo, we expressed TRPV4 in Caenorhabditis elegans sensory neurons and examined its ability to generate behavioral responses to sensory stimuli. C elegans ASH neurons function as polymodal sensory neurons that generate a characteristic escape behavior in response to mechanical, osmotic, or olfactory stimuli. These behaviors require the TRPV channel OSM-9 because osm-9 mutants do not avoid nose touch, high osmolarity, or noxious odors. Expression of mammalian TRPV4 in ASH neurons of osm-9 worms restored avoidance responses to hypertonicity and nose touch, but not the response to odorant repellents. Mutations known to reduce TRPV4 channel activity also reduced its ability to direct nematode avoidance behavior. TRPV4 function in ASH required the endogenous C. elegans osmotic and nose touch avoidance genes ocr-2, odr-3, osm-10, and glr-1, indicating that TRPV4 is integrated into the normal ASH sensory apparatus. The osmotic and mechanical avoidance responses of TRPV4- expressing animals were different in their sensitivity and temperature dependence from the responses of wild-type animals, suggesting that the TRPV4 channel confers its characteristic properties on the transgenic animals' behavior. These results provide evidence that TRPV4 can function as a component of an osmotic/mechanical sensor in vivo.
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收藏
页码:14531 / 14536
页数:6
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