title: A novel ion channel formed by interaction of TRPML3 with TRPV5.
abstract: TRPML3 and TRPV5 are members of the mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels. Based on sequence similarities of the pore forming regions and on structure-function evidence, we hypothesized that the pore forming domains of TRPML and TRPV5/TRPV6 channels have similarities that indicate possible functional interactions between these TRP channel subfamilies. Here we show that TRPML3 and TRPV5 associate to form a novel heteromeric ion channel. This novel conductance is detectable under conditions that do not activate either TRPML3 or TRPV5. It has pharmacological similarity with TRPML3 and requires functional TRPML3 as well as functional TRPV5. Single channel analyses revealed that TRPML3 and TRPV5 heteromers have different features than the respective homomers, and furthermore, that they occur in potentially distinct stoichiometric configurations. Based on overlapping expression of TRPML3 and TRPV5 in the kidney and the inner ear, we propose that TRPML3 and TRPV5 heteromers could have a biological function in these organs.
authors.affiliation: Department of Otolaryngology-HNS, Stanford University School of Medicine, Palo Alto, California, United States of America.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Guo
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
authors.forename: Lars
authors.initials: L
authors.lastname: Becker
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Ricci
authors.forename: Stefan
authors.initials: S
authors.lastname: Heller
mesh_terms: D004553:Electric Conductivity; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000378:metabolism; D050916:TRPV Cation Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C510642:MCOLN3 protein, human; D020033:Protein Isoforms; D021122:Protein Subunits; D050916:TRPV Cation Channels; C492239:TRPV5 protein, human; C120776:TRPV6 channel; D050051:Transient Receptor Potential Channels