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PMID: 12032305 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Subunit composition of mammalian transient receptor potential channels in living cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 11 ·2002-05-28 ·Pages 7461-6

Hofmann T, Schaefer M, Schultz G, Gudermann T

Abstract

Hormones, neurotransmitters, and growth factors give rise to calcium entry via receptor-activated cation channels that are activated downstream of phospholipase C activity. Members of the transient receptor potential channel (TRPC) family have been characterized as molecular substrates mediating receptor-activated cation influx. TRPC channels are assumed to be composed of multiple TRPC proteins. However, the cellular principles governing the assembly of TRPC proteins into homo- or heteromeric ion channels still remain elusive. By pursuing four independent experimental approaches--i.e., subcellular cotrafficking of TRPC subunits, differential functional suppression by dominant-negative subunits, fluorescence resonance energy transfer between labeled TRPC subunits, and coimmunoprecipitation--we investigate the combinatorial rules of TRPC assembly. Our data show that (i) TRPC2 does not interact with any known TRPC protein and (ii) TRPC1 has the ability to form channel complexes together with TRPC4 and TRPC5. (iii) All other TRPCs exclusively assemble into homo- or heterotetramers within the confines of TRPC subfamilies--e.g., TRPC4/5 or TRPC3/6/7. The principles of TRPC channel formation offer the conceptual framework to assess the physiological role of distinct TRPC proteins in living cells.

MeSH Terms
Calcium Channels/chemistry,genetics,metabolism Cell Line Cloning, Molecular Codon, Terminator Genes, Reporter Green Fluorescent Proteins Humans Ion Channels Luminescent Proteins/genetics Membrane Proteins Microscopy, Confocal Mutagenesis, Site-Directed Protein Subunits Recombinant Fusion Proteins/metabolism Reverse Transcriptase Polymerase Chain Reaction TRPC Cation Channels TRPM Cation Channels Transfection
Chemicals
Calcium Channels Codon, Terminator Ion Channels Luminescent Proteins Membrane Proteins Protein Subunits Recombinant Fusion Proteins TRPC Cation Channels TRPC2 protein, human TRPC7 protein, human TRPM Cation Channels TRPM2 protein, human transient receptor potential cation channel, subfamily C, member 1 Green Fluorescent Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hofmann Thomas
Institut für Pharmakologie und Toxikologie, Philipps-Universität Marburg, Karl-von-Frisch-Strasse 1, D-35033 Marburg, Germany.
Schaefer Michael
Schultz Günter
Gudermann Thomas
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.102596199
Published
2002-05-28
Pages
7461-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC124253
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.102596199 PMC Full Text View journal details
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