title: Impaired αGDI Function in the X-Linked Intellectual Disability: The Impact on Astroglia Vesicle Dynamics.
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-/Ymouse 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.
authors.affiliation: Celica Biomedical, Tehnološki park 24, 1000, Ljubljana, Slovenia.|Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000, Ljubljana, Slovenia.
authors.forename: Maja
authors.initials: M
authors.lastname: Potokar
authors.affiliation: Celica Biomedical, Tehnološki park 24, 1000, Ljubljana, Slovenia.|Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000, Ljubljana, Slovenia.
authors.forename: Jernej
authors.initials: J
authors.lastname: Jorgačevski
authors.affiliation: Celica Biomedical, Tehnološki park 24, 1000, Ljubljana, Slovenia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lacovich
authors.affiliation: Celica Biomedical, Tehnološki park 24, 1000, Ljubljana, Slovenia.|Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000, Ljubljana, Slovenia.|Biotechnical Faculty, University of Ljubljana, 1000, Ljubljana, Slovenia.
authors.forename: Marko
authors.initials: M
authors.lastname: Kreft
authors.affiliation: Celica Biomedical, Tehnološki park 24, 1000, Ljubljana, Slovenia.|Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000, Ljubljana, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Vardjan
authors.affiliation: Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Bianchi
authors.affiliation: Celica Biomedical, Tehnološki park 24, 1000, Ljubljana, Slovenia.|Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000, Ljubljana, Slovenia.|Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: D'Adamo
authors.affiliation: Celica Biomedical, Tehnološki park 24, 1000, Ljubljana, Slovenia. robert.zorec@mf.uni-lj.si.|Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000, Ljubljana, Slovenia. robert.zorec@mf.uni-lj.si.
authors.forename: Robert
authors.initials: R
authors.lastname: Zorec
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D004195:Disease Models, Animal; D011992:Endosomes / Q000378:metabolism; D020868:Gene Silencing; D050172:Genes, X-Linked; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics* / Q000378:metabolism; D008607:Intellectual Disability / Q000235:genetics*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics; D051381:Rats; D014162:Transfection
chemical_list: D020730:Guanine Nucleotide Dissociation Inhibitors
keywords: Astrocyte; Vesicle traffic; XLID; αGDI