抄録
TRPV4, a member of TRPV subfamily, is a nonselective cation channel that is activated by hypotonic stimulus, warm temperatures (about 25-34 °C) or chemical compounds such as 4α-PDD, and is expressed in various tissues. To investigate TRPV4 function in the epithelial tissue, we screened a cDNA library from epithelial cells to identify TRPV4 interacting protein using a yeast two-hybrid system. Sequence analysis revealed that one of the positive clones encodes a protein containing one PDZ and three LIM domains. We found that the N terminal region of TRPV4 bound to LIM domains of the PDZ-LIM protein. When both TRPV4 and the PDZ-LIM protein were co-expressed in HEK293 cells, patch-clamp analysis showed that 4α-PDD-evoked currents were larger than those observed in cells expressing TRPV4 alone. However, the increase in the 4α-PDD-evoked currents was profoundly decreased by PMA treatment in the cells expressing TRPV4 with the PDZ-LIM protein. These results suggest that the PDZ-LIM protein regulates TRPV4 activity by PKC activation. [J Physiol Sci. 2007;57 Suppl:S231]