期刊
JOURNAL OF CELL SCIENCE
卷 132, 期 23, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.238360
关键词
TRP ion channels; TRPC6; Mechanosensitive channels; Ion channel reconstitution; Mechanotransduction
类别
资金
- University of Newcastle PhD Scholarship
- University of New South Wales PhD Scholarship
- New South Wales Health Early-Mid Career (EMC) Fellowship
- National Health and Medical Research Council (NHMRC) of Australia
- NHMRC of Australia [APP1108013]
- National Institutes of Health [R01GM125629]
- United States-Israel Binational Science Foundation [2015221]
- American Heart Association [16SDG26700010, 15SDG25700146]
TRP channels of the transient receptor potential ion channel superfamily are involved in a wide variety of mechanosensory processes, including touch sensation, pain, blood pressure regulation, bone loading and detection of cerebrospinal fluid flow. However, in many instances it is unclear whether TRP channels are the primary transducers of mechanical force in these processes. In this study, we tested stretch activation of eleven TRP channels from six mammalian subfamilies. We found that these TRP channels were insensitive to short membrane stretches in cellular systems. Furthermore, we purified TRPC6 and demonstrated its insensitivity to stretch in liposomes, an artificial bilayer system free from cellular components. Additionally, we demonstrated that, when expressed in C. elegans neurons, mouse TRPC6 restores the mechanoresponse of a touch insensitive mutant but requires diacylglycerol for activation. These results strongly suggest that the mammalian members of the TRP ion channel family are insensitive to tension induced by cell membrane stretching and, thus, are more likely to be activated by cytoplasmic tethers or downstream components and to act as amplifiers of cellular mechanosensory signaling cascades.
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