Coassembly of Trp1 and Trp3 Proteins Generates
Diacylglycerol- and Ca2+-sensitive Cation Channels*
Birgit
Lintschinger
,
Monika
Balzer-Geldsetzer,
Tyagarajan
Baskaran,
Wolfgang F.
Graier§,
Christoph
Romanin¶,
Michael X.
Zhu
, and
Klaus
Groschner**
From the Departments of Pharmacology und Toxikology
and § Medical Biochemistry and Medical Molecular Biology,
University of Graz, Universitätsplatz 2, A-8010 Graz, Austria,
the ¶ Department of Biophysics, University of Linz, A-4040 Linz,
Austria, and the Neurobiotechnology Center, Ohio State
University, Columbus, Ohio 43210
To analyze the functional consequences of
coassembly of transient receptor potential 1 (Trp1) and Trp3 channel
proteins, we characterized membrane conductances and divalent cation
entry derived by separate overexpression and by coexpression of both Trp isoforms. Trp1 expression generated a
1-oleoyl-2-acetyl-sn-glycerol (OAG)-activated conductance
that was detectable only in Ca2+-free extracellular
solution. Trp3 expression gave rise to an OAG-activated conductance
that was suppressed but clearly detectable at physiological
Ca2+ concentrations. Coexpression of both species resulted
in a constitutively active, OAG-sensitive conductance, which exhibited
distinctive cation selectivity and high sensitivity to inhibition by
intracellular Ca2+. Trp1-expressing cells displayed only
modest carbachol-induced Ca2+ entry and lacked OAG-induced
Sr2+ entry, whereas Trp3-expressing cells responded to both
agents with a substantial divalent cation entry. Coexpression of Trp1 plus Trp3 suppressed carbachol-induced Ca2+ entry compared
with Trp3 expression and abolished OAG-induced Sr2+ entry
signals. We concluded that coassembly of Trp1 and Trp3 resulted
in the formation of oligomeric Trp channels that are subject to
regulation by phospholipase C and Ca2+. The distinguished
Ca2+ sensitivity of these Trp1/Trp3 hetero-oligomers
appeared to limit Trp-mediated Ca2+ signals and may be of
importance for negative feedback control of Trp function in mammalian cells.
*
This work was supported by the Fonds zur Foerderung der
Wissenschaftlichen Forschung, Spezial Forschungs Bereich (SFB)
Biomembranes F715 and P12667 (to K. G.), SFB Biomembranes F714 and
P12341 (to W. F. G.), and P12728 and Oesterreichische Nationalbank NB
7855 (to C. R.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
