title: ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory.
abstract: The Abl-interactor (Abi) family of adaptor proteins has been linked to signaling pathways involving the Abl tyrosine kinases and the Rac GTPase. Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dynamics in vitro. Here we demonstrate that Abi2 modulates cell morphogenesis and migration in vivo. Homozygous deletion of murine abi2 produced abnormal phenotypes in the eye and brain, the tissues with the highest Abi2 expression. In the absence of Abi2, secondary lens fiber orientation and migration were defective in the eye, without detectable defects in proliferation, differentiation, or apoptosis. These phenotypes were consistent with the localization of Abi2 at adherens junctions in the developing lens and at nascent epithelial cell adherens junctions in vitro. Downregulation of Abi expression by RNA interference impaired adherens junction formation and correlated with downregulation of the Wave actin-nucleation promoting factor. Loss of Abi2 also resulted in cell migration defects in the neocortex and hippocampus, abnormal dendritic spine morphology and density, and severe deficits in short- and long-term memory. These findings support a role for Abi2 in the regulation of cytoskeletal dynamics at adherens junctions and dendritic spines, which is critical for intercellular connectivity, cell morphogenesis, and cognitive functions.
authors.affiliation: Duke University Medical Center, Department of Pharmacology and Cancer Biology, Box 3813, Durham, NC 27710, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Grove
authors.forename: Galina
authors.initials: G
authors.lastname: Demyanenko
authors.forename: Asier
authors.initials: A
authors.lastname: Echarri
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Zipfel
authors.forename: Marisol E
authors.initials: ME
authors.lastname: Quiroz
authors.forename: Ramona M
authors.initials: RM
authors.lastname: Rodriguiz
authors.forename: Martin
authors.initials: M
authors.lastname: Playford
authors.forename: Shelby A
authors.initials: SA
authors.lastname: Martensen
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Robinson
authors.forename: William C
authors.initials: WC
authors.lastname: Wetsel
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Maness
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Pendergast
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D003712:Dendrites / Q000235:genetics; D049229:Dendritic Spines / Q000235:genetics*; D004285:Dogs; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D006367:HeLa Cells; D006624:Hippocampus / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007858:Learning; D007908:Lens, Crystalline / Q000196:embryology / Q000378:metabolism; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics*; D019579:Neocortex / Q000166:cytology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: C490756:Abi2 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering