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The Journal of Neuroscience, November 14, 2007, 27(46):12690-12699; doi:10.1523/JNEUROSCI.2381-07.2007

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Cellular/Molecular
Increased Expression of Golli Myelin Basic Proteins Enhances Calcium Influx into Oligodendroglial Cells

Pablo M. Paez, Vilma Spreuer, Vance Handley, Ji-Ming Feng, Celia Campagnoni, and Anthony T. Campagnoni

Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles Geffen Medical School, Los Angeles, California 90095

Correspondence should be addressed to Dr. Anthony T. Campagnoni, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles Geffen Medical School, Neuroscience Research Building, 635 Charles Young Drive, Los Angeles, CA 90095-7332. Email: acampagnoni{at}mednet.ucla.edu

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.

Key words: golli proteins; oligodendrocyte; calcium influx; process extension; voltage-gated calcium channels; myelin proteins

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Received May 24, 2007; revised Sept. 28, 2007; accepted Oct. 1, 2007.

Correspondence should be addressed to Dr. Anthony T. Campagnoni, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles Geffen Medical School, Neuroscience Research Building, 635 Charles Young Drive, Los Angeles, CA 90095-7332. Email: acampagnoni{at}mednet.ucla.edu

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