Golli protein negatively regulates store depletion-induced calcium influx in T cells.
Calcium influx is crucial for T cell activation and differentiation. The detailed regulation of this process remains unclear. We report here that golli protein, an alternatively spliced product of the myelin basic protein gene, plays a critical role in regulating calcium influx in T cells. Golli-deficient T cells were hyperproliferative and showed enhanced calcium entry upon T cell receptor stimulation. We further found that golli regulates calcium influx in T cells through the inhibition of the store depletion-induced calcium influx. Mutation of the myristoylation site on golli disrupted its association with the plasma membrane and reversed its inhibitory action on Ca2+ influx, indicating that membrane association of golli was essential for its inhibitory action. These results indicate that golli functions in a unique way to regulate T cell activation through a mechanism involving the modulation of the calcium homeostasis.
Feng
Ji-Ming
JM
Semel Institute of Neuroscience and Human Behavior, UCLA Geffen School of Medicine, 635 Charles Young Drive, Los Angeles, California 90095. Electronic address: jfeng@mednet.ucla.edu.
Hu
Yanhong K
YK
Semel Institute of Neuroscience and Human Behavior, UCLA Geffen School of Medicine, 635 Charles Young Drive, Los Angeles, California 90095.
Xie
Lai-Hua
LH
Department of Cardiology, UCLA Geffen School of Medicine, 635 Charles Young Drive, Los Angeles, California 90095.
Colwell
Christopher S
CS
Semel Institute of Neuroscience and Human Behavior, UCLA Geffen School of Medicine, 635 Charles Young Drive, Los Angeles, California 90095.
Shao
Xuesi M
XM
Department of Neurobiology, UCLA Geffen School of Medicine, 635 Charles Young Drive, Los Angeles, California 90095.
Sun
Xiao-Ping
XP
Department of Physiology, UCLA Geffen School of Medicine, 635 Charles Young Drive, Los Angeles, California 90095.
Chen
Boming
B
Department of Physiology, UCLA Geffen School of Medicine, 635 Charles Young Drive, Los Angeles, California 90095.
Tang
Hezhen
H
Semel Institute of Neuroscience and Human Behavior, UCLA Geffen School of Medicine, 635 Charles Young Drive, Los Angeles, California 90095.
Campagnoni
Anthony T
AT
Semel Institute of Neuroscience and Human Behavior, UCLA Geffen School of Medicine, 635 Charles Young Drive, Los Angeles, California 90095. Electronic address: acampagnoni@mednet.ucla.edu.
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D002462:Cell Membrane / Q000737:chemistry; D015536:Down-Regulation; D004789:Enzyme Activation; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D015220:Calcium Channels; D007376:Interleukin-2; C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D020929:Mitogen-Activated Protein Kinase Kinases; D002118:Calcium