Article
- The EMBO Journal (2006) 25, 1611 - 1622
- doi:10.1038/sj.emboj.7601053
Published online: 6 April 2006
Subject Categories:
SH3P7/mAbp1 deficiency leads to tissue and behavioral abnormalities and impaired vesicle transport
Sabine Connert1,ab, Simone Wienand2,a, Cora Thiel2,a, Maria Krikunova3,c, Nataliya Glyvuk3, Yaroslav Tsytsyura3, Denise Hilfiker-Kleiner4, Jörg W Bartsch5,d, Jürgen Klingauf3 and Jürgen Wienands2
- Department of Biochemistry and Molecular Immunology, University of Bielefeld, Bielefeld, Germany
- Cellular and Molecular Immunology, Medical Faculty of Georg-August-University, Göttingen, Germany
- Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
- Cardiology and Angiology, Medical School Hannover, Hannover, Germany
- Department of Developmental Biology and Molecular Pathology, University of Bielefeld, Bielefeld, Germany
Correspondence to:
Jürgen Wienands, Department of Cellular and Molecular Immunology, Medical Faculty of the Georg-August-University of Göttingen, Humboldtallee 34, 37073 Göttingen, Germany. Tel.: +49 551 39 5812; Fax: +49 551 39 5843; E-mail: jwienan@uni-goettingen.de
aThese authors contributed equally to this work
bPresent address: Clinical Research Unit for Rheumatology, University Hospital Freiburg, Freiburg, Germany
cPresent address: Institute of Experimental Physics, University of Hamburg, Hamburg, Germany
dPresent address: Department of Biochemistry, King's College London, London, UK
Received 16 August 2005; Accepted 28 February 2006
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.
Keywords:
- actin-binding proteins,
- clathrin-mediated endocytosis,
- fluorescence microscopy,
- SH3P7/mAbp1 deficiency,
- synaptic vesicle recycling
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