TY - JOUR T1 - Identification of a Tetramerization Domain in the C Terminus of the Vanilloid Receptor JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5307 LP - 5314 DO - 10.1523/JNEUROSCI.0202-04.2004 VL - 24 IS - 23 AU - Nuria García-Sanz AU - Asia Fernández-Carvajal AU - Cruz Morenilla-Palao AU - Rosa Planells-Cases AU - Emmanuel Fajardo-Sánchez AU - Gregorio Fernández-Ballester AU - Antonio Ferrer-Montiel Y1 - 2004/06/09 UR - http://www.jneurosci.org/content/24/23/5307.abstract N2 - TRPV1 (transient receptor potential vanilloid receptor subtype 1) is a member of the TRP channel family gated by vanilloids, protons, and heat. Structurally, TRPV1 appears to be a tetramer formed by the assembly of four identical subunits around a central aqueous pore. The molecular determinants that govern its subunit oligomerization remain elusive. Here, we report the identification of a segment comprising 684Glu-721Arg (referred to as the TRP-like domain) in the C terminus of TRPV1 as an association domain (AD) of the protein. Purified recombinant C terminus of TRPV1 (TRPV1-C) formed discrete and stable multimers in vitro. Yeast two-hybrid and pull-down assays showed that self-association of the TRPV1-C is blocked when segment 684Glu-721Arg is deleted. Biochemical and immunological analysis indicate that removal of the AD from full-length TRPV1 monomers blocks the formation of stable heteromeric assemblies with wild-type TRPV1 subunits. Deletion of the AD in a poreless TRPV1 subunit suppressed its robust dominant-negative phenotype. Together, these findings are consistent with the tenet that the TRP-like domain in TRPV1 is a molecular determinant of the tetramerization of receptor subunits into functional channels. Our observations suggest that the homologous TRP domain in the TRP protein family may function as a general, evolutionary conserved AD involved in subunit multimerization. ER -