title: SH3P7/mAbp1 deficiency leads to tissue and behavioral abnormalities and impaired vesicle transport.
abstract: The intracellular adaptor protein SH3P7 is the mammalian ortholog of yeast actin-binding protein 1 and thus alternatively named as mAbp1 (or HIP55). Structural properties, biochemical analysis of its interaction partners and siRNA studies implicated mAbp1 as an accessory protein in clathrin-mediated endocytosis (CME). Here, we describe the generation and characterization of mice deficient for SH3P7/mAbp1 owing to targeted gene disruption in embryonic stem cells. Mutant animals are viable and fertile without obvious deficits during the first weeks of life. Abnormal structure and function of organs including the spleen, heart, and lung is observed at about 3 months of age in both heterozygous and homozygous mouse mutants. A moderate reduction of both receptor-mediated and synaptic endocytosis is observed in embryonic fibroblasts and in synapses of hippocampal neurons, respectively. Recycling of synaptic vesicles in hippocampal boutons is severely impaired and delayed four-fold. The presynaptic defect of SH3P7/mAbp1 mouse mutants is associated with their constricted physical capabilities and disturbed neuromotoric behaviour. Our data reveal a nonredundant role of SH3P7/mAbp1 in CME and places its function downstream of vesicle fission.
authors.affiliation: Department of Biochemistry and Molecular Immunology, University of Bielefeld, Bielefeld, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Connert
authors.forename: Simone
authors.initials: S
authors.lastname: Wienand
authors.forename: Cora
authors.initials: C
authors.lastname: Thiel
authors.forename: Maria
authors.initials: M
authors.lastname: Krikunova
authors.forename: Nataliya
authors.initials: N
authors.lastname: Glyvuk
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Tsytsyura
authors.forename: Denise
authors.initials: D
authors.lastname: Hilfiker-Kleiner
authors.forename: Jörg W
authors.initials: JW
authors.lastname: Bartsch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klingauf
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wienands
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis; D005347:Fibroblasts / Q000502:physiology; D006330:Heart Defects, Congenital / Q000235:genetics; D006624:Hippocampus / Q000648:ultrastructure; D008168:Lung / Q000002:abnormalities; D008561:Membrane Fusion; D051379:Mice; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009043:Motor Activity / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D011656:Pulmonary Emphysema / Q000235:genetics; D013154:Spleen / Q000002:abnormalities; D013572:Synaptic Vesicles / Q000235:genetics / Q000502:physiology*; D018909:src Homology Domains / Q000235:genetics / Q000502:physiology*
chemical_list: C485512:Dbnl protein, mouse; D008840:Microfilament Proteins