Depletion of intracellular Ca2+ stores stimulates the translocation of vanilloid transient receptor potential 4-c1 heteromeric channels to the plasma membrane.
OBJECTIVE
To examine the effect of Ca(2+) store depletion on the translocation of vanilloid transient receptor potential (TRPV) 4-C1 heteromeric channels to the plasma membrane.


RESULTS
Vesicular trafficking is a key mechanism for controlling the surface expression of TRP channels in the plasma membrane, where they perform their function. TRP channels in vivo are often composed of heteromeric subunits. Experiments using total internal fluorescence reflection microscopy and biotin surface labeling show that Ca(2+) store depletion enhanced TRPV4-C1 translocation into the plasma membrane in human embryonic kidney 293 cells that were coexpressed with TRPV4 and canonical transient receptor potential 1 (TRPC1). Fluorescent Ca(2+) measurement and patch clamp studies demonstrated that Ca(2+) store depletion enhanced 4α-PDD-stimulated Ca(2+) influx and cation current. The translocation required stromal interacting molecule 1 (STIM1). TRPV4-C1 heteromeric channels were more favorably translocated to the plasma membrane than TRPC1 or TRPV4 homomeric channels. Similar results were obtained in native vascular endothelial cells.


CONCLUSIONS
Ca(2+) store depletion stimulates the insertion of TRPV4-C1 heteromeric channels into the plasma membrane, resulting in an augmented Ca(2+) influx in response to flow in the human embryonic kidney cell overexpression system and native endothelial cells.
Ma
Xin
X
Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
Cao
Jingyuan
J
Luo
Jianhong
J
Nilius
Bernd
B
Huang
Yu
Y
Ambudkar
Indu S
IS
Yao
Xiaoqiang
X
D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology*; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000502:physiology; D042783:Endothelial Cells; D057809:HEK293 Cells; D006801:Humans; D018408:Patch-Clamp Techniques; D050916:TRPV Cation Channels / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology
D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D002118:Calcium