PubMed 22961981

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPM , TRPM3 , TRPM8

Title: Alternative splicing of a protein domain indispensable for function of transient receptor potential melastatin 3 (TRPM3) ion channels.

Authors: Julia Frühwald, Julia Camacho Londoño, Sandeep Dembla, Stefanie Mannebach, Annette Lis, Anna Drews, Ulrich Wissenbach, Johannes Oberwinkler, Stephan E Philipp

Journal, date & volume: J. Biol. Chem., 2012 Oct 26 , 287, 36663-72

PubMed link:

TRPM3 channels form ionotropic steroid receptors in the plasma membrane of pancreatic β and dorsal root ganglion cells and link steroid hormone signaling to insulin release and pain perception, respectively. We identified and compared the function of a number of TRPM3 splice variants present in mouse, rat and human tissues. We found that variants lacking a region of 18 amino acid residues display neither Ca(2+) entry nor ionic currents when expressed alone. Hence, splicing removes a region that is indispensable for channel function, which is called the ICF region. TRPM3 variants devoid of this region (TRPM3ΔICF), are ubiquitously present in different tissues and cell types where their transcripts constitute up to 15% of the TRPM3 isoforms. The ICF region is conserved throughout the TRPM family, and its presence in TRPM8 proteins is also necessary for function. Within the ICF region, 10 amino acid residues form a domain essential for the formation of operative TRPM3 channels. TRPM3ΔICF variants showed reduced interaction with other TRPM3 isoforms, and their occurrence at the cell membrane was diminished. Correspondingly, coexpression of ΔICF proteins with functional TRPM3 subunits not only reduced the number of channels but also impaired TRPM3-mediated Ca(2+) entry. We conclude that TRPM3ΔICF variants are regulatory channel subunits fine-tuning TRPM3 channel activity.