Increased expression of golli myelin basic proteins enhances calcium influx into oligodendroglial cells.
The myelin basic protein (MBP) gene encodes two families of proteins: the classic MBP constituents of myelin and the golli-MBPs, the function of which is less well understood. Previous work suggests that golli proteins may play a role in Ca2+ homeostasis in oligodendrocytes (OLs) and in T-cells. Overexpression of golli in OL cell lines induces elaboration of sheets and processes. Live imaging of these cells revealed a rapid retraction of the processes and sheets after depolarization with high K+. This phenomenon was associated with a significant increase in [Ca2+]int without changes in cell viability. The results indicated that golli produced its effect through Ca2+ influx, rather than Ca2+ release from intracellular stores. Furthermore, a specific [Ca2+]int chelator (BAPTA) or Cd2+, a specific blocker of voltage-operated Ca2+ channels, abolished the ability of golli to promote process extension in a dose-dependent manner. Analysis of the golli protein identified a myristoylation site at the C terminus of the golli domain, which was essential for the action of golli on Ca2+ influx, suggesting that binding of golli to the plasma membrane is important for modulating Ca2+ homeostasis. High-resolution spatiotemporal analysis along N19 processes revealed higher-amplitude local Ca2+ influx in regions with elevated levels of golli. These findings suggest a key role for golli proteins in regulating voltage-gated Ca2+ channels in OLs during process remodeling. Our observations are consistent with the hypothesis that golli proteins, as a part of a protein complex, modulate Ca2+ influx at the plasma membrane and along OL processes.
Paez
Pablo M
PM
Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles Geffen Medical School, Los Angeles, California 90095, USA.
Spreuer
Vilma
V
Handley
Vance
V
Feng
Ji-Ming
JM
Campagnoni
Celia
C
Campagnoni
Anthony T
AT
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D022081:Cell Surface Extensions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D002121:Calcium Channel Blockers; D015220:Calcium Channels; C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D002118:Calcium