Evidence for an interaction between Golli and STIM1 in store-operated calcium entry.
SOCCs (store-operated Ca(2+) channels) are highly selective ion channels that are activated upon release of Ca(2+) from intracellular stores to regulate a multitude of diverse cellular functions. It was reported previously that Golli-BG21, a member of the MBP (myelin basic protein) family of proteins, regulates SOCE (store-operated Ca(2+) entry) in T-cells and oligodendrocyte precursor cells, but the underlying mechanism for this regulation is unknown. In the present study we have discovered that Golli can directly interact with the ER (endoplasmic reticulum) Ca(2+)-sensing protein STIM1 (stromal interaction molecule 1). Golli interacts with the C-terminal domain of STIM1 in both in vitro and in vivo binding assays and this interaction may be modulated by the intracellular Ca(2+) concentration. Golli also co-localizes with full-length STIM1 and Orai1 complexes in HeLa cells following Ca(2+) store depletion. Overexpression of Golli reduces SOCE in HeLa cells, but this inhibition is overcome by overexpressing STIM1. We therefore suggest that Golli binds to STIM1-Orai1 complexes to negatively regulate the activity of SOCCs.
Walsh
Ciara M
CM
University of Liverpool, UK.
Doherty
Mary K
MK
Tepikin
Alexei V
AV
Burgoyne
Robert D
RD
D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D004676:Myelin Basic Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D000071737:Stromal Interaction Molecule 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D008164:Luminescent Proteins; C499048:MBP protein, human; D008565:Membrane Proteins; D004676:Myelin Basic Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D014157:Transcription Factors; D002118:Calcium