TRPC6

Transient receptor potential cation channel, subfamily C, member 6
Identifiers
Symbols	TRPC6 ; FSGS2; TRP6
External IDs	OMIM: 603652 HomoloGene: 37944 IUPHAR: 491 GeneCards: TRPC6 Gene
Gene ontology Molecular function • protein binding • store-operated calcium channel activity • inositol 1,4,5 trisphosphate binding Cellular component • cytoplasm • cytosol • plasma membrane • integral component of plasma membrane • membrane • slit diaphragm Biological process • cation transport • manganese ion transport • positive regulation of cytosolic calcium ion concentration • axon guidance • aging • blood coagulation • platelet activation • positive regulation of ion transmembrane transporter activity • ion transmembrane transport • cytosolic calcium ion homeostasis • positive regulation of calcium ion transport • transmembrane transport • cellular response to hydrogen peroxide • calcium ion transmembrane transport • cellular response to hypoxia Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7225	22068
Ensembl	ENSG00000137672	ENSMUSG00000031997
UniProt	Q9Y210	Q61143
RefSeq (mRNA)	NM_004621	NM_001282086
RefSeq (protein)	NP_004612	NP_001269015
Location (UCSC)	Chr 11: 101.45 – 101.87 Mb	Chr 9: 8.54 – 8.68 Mb
PubMed search

Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential ion channel. It has been associated with depression and anxiety (see below), as well as with focal segmental glomerulosclerosis (FSGS).^[1]

Interactions

TRPC6 has been shown to interact with:

• FYN,^[2]
• TRPC2,^[3] and
• TRPC3.^[4]

Ligands

Two of the primary active constituents responsible for the antidepressant and anxiolytic benefits of Hypericum perforatum, also known as St. John's Wort, are hyperforin and adhyperforin.^[5][6] These compounds are inhibitors of the reuptake of serotonin, norepinephrine ,dopamine, γ-aminobutyric acid, and glutamate, and they exert these effects by binding to and activating TRPC6.^[6][7] Activation of TRPC6 induces the entry of Ca²⁺ and Na⁺ into the cell, which results in the inhibition of reuptake.^[7]

References

1. Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, Daskalakis N, Kwan SY, Ebersviller S, Burchette JL, Pericak-Vance MA, Howell DN, Vance JM, Rosenberg PB (2005). "A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis". Science 308 (5729): 1801–4. doi:10.1126/science.1106215. PMID 15879175.
2. Hisatsune C, Kuroda Y, Nakamura K, Inoue T, Nakamura T, Michikawa T, Mizutani A, Mikoshiba K (Apr 2004). "Regulation of TRPC6 channel activity by tyrosine phosphorylation". J. Biol. Chem. 279 (18): 18887–94. doi:10.1074/jbc.M311274200. PMID 14761972.
3. Chu X, Tong Q, Cheung JY, Wozney J, Conrad K, Mazack V, Zhang W, Stahl R, Barber DL, Miller BA (March 2004). "Interaction of TRPC2 and TRPC6 in erythropoietin modulation of calcium influx". J. Biol. Chem. 279 (11): 10514–22. doi:10.1074/jbc.M308478200. PMID 14699131.
4. Hofmann T, Schaefer M, Schultz G, Gudermann T (May 2002). "Subunit composition of mammalian transient receptor potential channels in living cells". Proc. Natl. Acad. Sci. U.S.A. 99 (11): 7461–6. doi:10.1073/pnas.102596199. PMC 124253. PMID 12032305.
5. Müller WE, Singer A, Wonnemann M (2001). "Hyperforin--antidepressant activity by a novel mechanism of action". Pharmacopsychiatry. 34 Suppl 1: S98–102. doi:10.1055/s-2001-15512. PMID 11518085.
6. Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Müller WE (1998). "Hyperforin as a possible antidepressant component of hypericum extracts". Life Sci. 63 (6): 499–510. doi:10.1016/S0024-3205(98)00299-9. PMID 9718074.
7. Leuner K, Kazanski V, Müller M, Essin K, Henke B, Gollasch M, Harteneck C, Müller WE (December 2007). "Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels". FASEB J. 21 (14): 4101–11. doi:10.1096/fj.07-8110com. PMID 17666455.

Further reading

• Heiner I, Eisfeld J, Lückhoff A (2004). "Role and regulation of TRP channels in neutrophil granulocytes". Cell Calcium 33 (5-6): 533–40. doi:10.1016/S0143-4160(03)00058-7. PMID 12765698.
• Walz G (2005). "Slit or pore? A mutation of the ion channel TRPC6 causes FSGS". Nephrol. Dial. Transplant. 20 (9): 1777–9. doi:10.1093/ndt/gfh961. PMID 15998650.
• Clapham DE, Julius D, Montell C, Schultz G (2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100.
• Schlöndorff JS, Pollak MR (2006). "TRPC6 in glomerular health and disease: what we know and what we believe". Semin. Cell Dev. Biol. 17 (6): 667–74. doi:10.1016/j.semcdb.2006.11.003. PMC 2705932. PMID 17116414.
• Dietrich A, Gudermann T (2007). "TRPC6". Handb Exp Pharmacol. Handbook of Experimental Pharmacology 179 (179): 125–41. doi:10.1007/978-3-540-34891-7_7. ISBN 978-3-540-34889-4. PMID 17217054.

External links

• TRPC6 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)