Impaired αGDI Function in the X-Linked Intellectual Disability: The Impact on Astroglia Vesicle Dynamics

M Potokar, J Jorgačevski, V Lacovich, M Kreft, N Vardjan, V Bianchi, P D'Adamo, R Zorec

Research output: Contribution to journalArticle

Abstract

X-linked non-syndromic intellectual disability (XLID) is a common mental disorder recognized by cognitive and behavioral deficits. Mutations in the brain-specific αGDI, shown to alter a subset of RAB GTPases redistribution in cells, are linked to XLID, likely via changes in vesicle traffic in neurons. Here, we show directly that isolated XLID mice astrocytes, devoid of pathologic tissue environment, exhibit vesicle mobility deficits. Contrary to previous studies, we show that astrocytes express two GDI proteins. The siRNA-mediated suppression of expression of αGDI especially affected vesicle dynamics. A similar defect was recorded in astrocytes from the Gdi1-/Y mouse model of XLID and in astrocytes with recombinant mutated human XLID αGDI. Endolysosomal vesicles studied here are involved in the release of gliosignaling molecules as well as in regulating membrane receptor density; thus, the observed changes in astrocytic vesicle mobility may, over the long time-course, profoundly affect signaling capacity of these cells, which optimize neural activity. © 2016 Springer Science+Business Media New York
Original languageEnglish
Pages (from-to)2458-2468
Number of pages11
JournalMolecular Neurobiology
Volume54
Issue number4
DOIs
Publication statusPublished - 2017

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    Potokar, M., Jorgačevski, J., Lacovich, V., Kreft, M., Vardjan, N., Bianchi, V., D'Adamo, P., & Zorec, R. (2017). Impaired αGDI Function in the X-Linked Intellectual Disability: The Impact on Astroglia Vesicle Dynamics. Molecular Neurobiology, 54(4), 2458-2468. https://doi.org/10.1007/s12035-016-9834-1