Chemico-genetic identification of drebrin as a regulator of calcium responses.
Store-operated calcium channels are plasma membrane Ca(2+) channels that are activated by depletion of intracellular Ca(2+) stores, resulting in an increase in intracellular Ca(2+) concentration, which is maintained for prolonged periods in some cell types. Increases in intracellular Ca(2+) concentration serve as signals that activate a number of cellular processes, however, little is known about the regulation of these channels. We have characterized the immuno-suppressant compound BTP, which blocks store-operated channel mediated calcium influx into cells. Using an affinity purification scheme to identify potential targets of BTP, we identified the actin reorganizing protein, drebrin, and demonstrated that loss of drebrin protein expression prevents store-operated channel mediated Ca(2+) entry, similar to BTP treatment. BTP also blocks actin rearrangements induced by drebrin. While actin cytoskeletal reorganization has been implicated in store-operated calcium channel regulation, little is known about actin-binding proteins that are involved in this process, or how actin regulates channel function. The identification of drebrin as a mediator of this process should provide new insight into the interaction between actin rearrangement and store-operated channel mediated calcium influx.
Mercer
Jason C
JC
Center for Molecular Immunology & Infectious Disease, Department of Veterinary & Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA.
Qi
Qian
Q
Mottram
Laurie F
LF
Law
Mankit
M
Bruce
Danny
D
Iyer
Archana
A
Morales
J Luis
JL
Yamazaki
Hiroyuki
H
Shirao
Tomoaki
T
Peterson
Blake R
BR
August
Avery
A
D000199:Actins / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D019169:Jurkat Cells; D008239:Lysine; D009479:Neuropeptides / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D011720:Pyrazoles / Q000737:chemistry / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
D000199:Actins; D015220:Calcium Channels; D009479:Neuropeptides; D011720:Pyrazoles; D034741:RNA, Small Interfering; C053386:drebrins; C031280:pyrazole; D008239:Lysine; D002118:Calcium