Author/Editor     Potokar, Maja; Jorgačevski, Jernej; Lacovich, Valentina; Kreft, Marko; Vardjan, Nina; Bianchi, Veronica; D'Adamo, Patrizia; Zorec, Robert
Title     Impaired [alpha]GDI function in the X-linked intellectual disability
Type     članek
Publication year     2016
ISSN     0893-7648 - Molecular neurobiology
Language     eng
Abstract     X-linked non-syndromic intellectual disability (XLID) is a common mental disorder recognized by cognitive and behavioral deficits. Mutations in the brain-specific [alpha]GDI, 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 [alpha]GDI 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 [alpha]GDI. 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.
Keywords     XLID
alfaGDI
eksocitoza
XLID
alphaGDI
astrocyte