A novel ion channel formed by interaction of TRPML3 with TRPV5.

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.