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Activation of sodium‐dependent glutamate transporters regulates the morphological aspects of oligodendrocyte maturation via signaling through calcium/calmodulin‐dependent kinase IIβ's actin‐binding/‐stabilizing domain
Author(s) -
MartinezLozada Zila,
Waggener Christopher T.,
Kim Karam,
Zou Shiping,
Knapp Pamela E.,
Hayashi Yasunori,
Ortega Arturo,
Fuss Babette
Publication year - 2014
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22699
Subject(s) - biology , glutamate receptor , microbiology and biotechnology , oligodendrocyte , actin cytoskeleton , calmodulin , biochemistry , cytoskeleton , neuroscience , central nervous system , myelin , cell , receptor , enzyme
Signaling via the major excitatory amino acid glutamate has been implicated in the regulation of various aspects of the biology of oligodendrocytes, the myelinating cells of the central nervous system (CNS). In this respect, cells of the oligodendrocyte lineage have been described to express a variety of glutamate‐responsive transmembrane proteins including sodium‐dependent glutamate transporters. The latter have been well characterized to mediate glutamate clearance from the extracellular space. However, there is increasing evidence that they also mediate glutamate‐induced intracellular signaling events. Our data presented here show that the activation of oligodendrocyte expressed sodium‐dependent glutamate transporters, in particular GLT‐1 and GLAST, promotes the morphological aspects of oligodendrocyte maturation. This effect was found to be associated with a transient increase in intracellular calcium levels and a transient phosphorylation event at the serine (S) 371 site of the calcium sensor calcium/calmodulin‐dependent kinase type IIβ (CaMKIIβ). The potential regulatory S 371 site is located within CaMKIIβ's previously defined actin‐binding/‐stabilizing domain, and phosphorylation events within this domain were identified in our studies as a requirement for sodium‐dependent glutamate transporter‐mediated promotion of oligodendrocyte maturation. Furthermore, our data provide good evidence for a role of these phosphorylation events in mediating detachment of CaMKIIβ from filamentous (F)‐actin, and hence allowing a remodeling of the oligodendrocyte's actin cytoskeleton. Taken together with our recent findings, which demonstrated a crucial role of CaMKIIβ in regulating CNS myelination in vivo , our data strongly suggest that a sodium‐dependent glutamate transporter–CaMKIIβ–actin cytoskeleton axis plays an important role in the regulation of oligodendrocyte maturation and CNS myelination. GLIA 2014;62:1543–1558