Title : Trafficking and assembly of the cold-sensitive
TRPM8 channel
Abstract :
- TRPM (transient receptor potential melastatin-like) channels are distinct from many other members of the transient receptor potential family in regard to their overall size (>1000 amino acids), the lack of N-terminal ankyrin-like repeats, and hydrophobicity predictions that may allow for more than six transmembrane regions
- Common to each TRPM member is a prominent C-terminal coiled coil region
- Here we have shown that TRPM8 channels assemble as multimers using the putative coiled coil region within the intracellular C terminus and that this assembly can be disturbed by a single point mutation within the coiled coil region
- This mutant neither gives rise to functional channels nor do its subunits interact or form protein complexes that correspond to a multimer
- However, they are still transported to the plasma membrane
- Furthermore, wild-type currents can be suppressed by expressing the membrane-attached C-terminal region of TRPM8
- To separate assembly from trafficking, we investigated the maturation of TRPM8 protein by identifying and mutating the relevant N-linked glycosylation site and showing that glycosylation is neither essential for multimerization nor for transport to the plasma membrane per se but appears to facilitate efficient multimerization and transport