期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 285, 期 1, 页码 731-740出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.052548
关键词
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资金
- National Institutes of Health [R01GM081340]
- American Heart Association [0335134N]
- Klingenstein Award
- McKnight Scholar Award
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM081340] Funding Source: NIH RePORTER
Transient receptor potential vanilloid (TRPV) channels, which include the thermosensitive TRPV1-V4, have large cytoplasmic regions flanking the transmembrane domain, including an N-terminal ankyrin repeat domain. We show that a multiligand binding site for ATP and calmodulin previously identified in the TRPV1 ankyrin repeat domain is conserved in TRPV3 and TRPV4, but not TRPV2. Accordingly, TRPV2 is insensitive to intracellular ATP, while, as previously observed with TRPV1, a sensitizing effect of ATP on TRPV4 required an intact binding site. In contrast, ATP reduced TRPV3 sensitivity and potentiation by repeated agonist stimulations. Thus, ATP and calmodulin, acting through this conserved binding site, are key players in generating the different sensitivity and adaptation profiles of TRPV1, TRPV3, and TRPV4. Our results suggest that competing interactions of ATP and calmodulin influence channel sensitivity to fluctuations in calcium concentration and perhaps even metabolic state. Different feedback mechanisms likely arose because of the different physiological stimuli or temperature thresholds of these channels.
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