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NMDA receptor NR2B subunit over‐expression increases cerebellar granule cell migratory activity
Author(s) -
Tárnok Krisztián,
Czöndör Katalin,
Jelitai Márta,
Czirók András,
Schlett Katalin
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.05051.x
Subject(s) - granule cell , cerebellum , protein subunit , nmda receptor , microbiology and biotechnology , granule (geology) , biology , glutamate receptor , mutant , receptor , chemistry , biochemistry , neuroscience , central nervous system , gene , paleontology , dentate gyrus
Glutamate acting on NMDA receptors (NMDARs) is known to influence cerebellar granule cell migration. Subunit composition of NMDARs in granule cells changes characteristically during development: NR2B subunit containing receptors are abundant during migration towards the internal granule cell layer but are gradually replaced by NR2A and/or NR2C subunits once the final position is reached. Cerebellar granule cell migration was investigated using mutant mouse lines either with a deletion of the NR2C gene (NR2C −/− mice) or expressing NR2B instead of the NR2C subunit (NR2C‐2B mice). BrdU‐labeling revealed that over‐expression of NR2B increased granule cell translocation in vivo , while the lack of NR2C subunit did not have any detectable effects on cell migration. Cellular composition of wild‐type and mutant dissociated cerebellar granule cell cultures isolated from 10‐day‐old cerebella were similar, but NR2C‐2B cultures had elevated level of NR2B subunits and intracellular Ca 2+ imaging revealed higher sensitivity towards the addition of NR2B‐selective antagonist in vitro . Time‐lapse videomicroscopic observations revealed that average migratory velocity and the proportion of translocating cell bodies were significantly higher in NR2C‐2B than in wild‐type cultures. Our results provide evidence that NR2B‐containing NMDARs can have specialized roles during granule cell migration and can increase migratory speed.