TRP genes: candidates for nonselective cation channels and store-operated channels in insulin-secreting cells.
Nonselective cation channels may play a role in insulin secretion by regulating pancreatic beta-cell plasma membrane potential, Ca(2+) homeostasis, and thereby glucose signaling. Transient receptor potential channel (TRPC)-related genes encode nonselective cation channels, some of which are similar to those described for beta-cells. Some TRPC-like channels are activated via G-protein--coupled mechanisms, some have been reported to be calcium-store-operated channels (SOC), and others are activated by novel signaling molecules or are sensitive to pressure and osmotic strength. Here we report the cloning and expression of mSTRPC4 from a mouse insulinoma cDNA library. mSTRPC4 encoded a protein of 97 kd, expressed in both endocrine cells and the brain. Stable cell lines expressing mSTRPC4 showed abundant mSTRPC4 protein, but no reproducible currents could be detected. mSTRPC4 therefore probably functions as a heteromultimer. We also report that LTRPC2, a G-protein and adenosine 5'-diphosphoribose (ADPR)-activated nonselective cation channel, is also expressed in human islets. TRPC-like channels may provide a pathway for depolarization or Ca(2+) entry in beta-cells and may be interesting targets for manipulating beta-cell function.
Qian
Feng
F
Department of Neurobiology, Physiology, and Pharmacology, the University of Chicago, Chicago, Illinois, USA.
Huang
Ping
P
Ma
Li
L
Kuznetsov
Andrey
A
Tamarina
Natalia
N
Philipson
Louis H
LH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D003001:Cloning, Molecular; D015870:Gene Expression / Q000502:physiology; D015723:Gene Library; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D002412:Cations; D007328:Insulin; D007473:Ion Channels; D008565:Membrane Proteins; D012333:RNA, Messenger; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; C498502:Trpc7 protein, mouse; D002118:Calcium