New Light on TRP and TRPL
- Departments of Biological Chemistry and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Abstract
Store-operated Ca2+ entry, a mode of Ca2+influx activated by depletion of Ca2+ from the internal stores, has been detected in a wide variety of cell types and may be the primary mechanism for Ca2+ entry in nonexcitable cells. Nevertheless, until recently, no candidate store-operated channel (SOC) had been identified molecularly. Through the serendipity ofDrosophila genetics, a candidate SOC, referred to as Transient Receptor Potential (TRP), has been identified that is essential for the light-induced cation conductance in photoreceptor cells. A combination of in vitro and in vivo studies has provided strong evidence that TRP is a bona fide SOC. Moreover, TRP forms a supramolecular complex, proposed to be critical for feedback regulation and/or activation, that includes rhodopsin, phospholipase C, protein kinase C, calmodulin, and the PDZ domain-containing protein, INAD. INAD seems to be a scaffolding protein that links TRP with several of these other proteins in the complex. TRP also complexes with a related channel subunit, TRP-like, to form a heteromultimer with conductance characteristics distinct from those of TRP or TRP-like homomultimers. A family of proteins related to TRP is conserved from Caenorhabditiselegans to humans, and recent evidence indicates that at least some of these proteins are SOCs. The human TRP-related proteins may mediate many of the store-operated conductances that have been identified previously in a plethora of human cells.
Footnotes
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Send reprint requests to: Dr. Craig Montell (408 WBSB), Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205. E-mail:craig.montell{at}qmail.bs.jhu.edu
- Abbreviations:
- SOCE
- store-operated calcium entry
- ERG
- electroretinogram recording
- ICRAC
- calcium release-activated calcium current
- IP3
- inositol-1,3,5-trisphosphate
- IP3R
- inositol-1,3,5-trisphosphate receptor
- PLC
- phospholipase C-β
- RH1
- rhodopsin
- SOC
- store-operated channel
- TRP
- transient receptor potential
- TRPL
- transient receptor potential-like
- TRPR
- transient receptor potential-related channel
- INAD
- inactivation no afterpotential D
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- Accepted August 11, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
