Syndapin I, a synaptic dynamin-binding protein that associates with the neural Wiskott-Aldrich syndrome protein

• Published in: Molecular biology of the cell 1999-02, Vol.10 (2), p.501-513
• Main Authors: Qualmann, B, Roos, J, DiGregorio, P J, Kelly, R B
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Base Sequence; Brain - metabolism; Carrier Proteins; Cloning, Molecular; Cytoskeletal Proteins; DNA Primers - genetics; DNA, Complementary - genetics; Dynamin I; Dynamins; GTP Phosphohydrolases - metabolism; Humans; Macromolecular Substances; Molecular Sequence Data; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; PC12 Cells; Phosphoric Monoester Hydrolases - metabolism; Rats; src Homology Domains; Synaptic Vesicles - metabolism; Wiskott-Aldrich Syndrome - metabolism; Wiskott-Aldrich Syndrome Protein, Neuronal
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.10.2.501

The GTPase dynamin has been clearly implicated in clathrin-mediated endocytosis of synaptic vesicle membranes at the presynaptic nerve terminal. Here we describe a novel 52-kDa protein in rat brain that binds the proline-rich C terminus of dynamin. Syndapin I (synaptic, dynamin-associated protein I) is highly enriched in brain where it exists in a high molecular weight complex. Syndapin I can be involved in multiple protein-protein interactions via a src homology 3 (SH3) domain at the C terminus and two predicted coiled-coil stretches. Coprecipitation studies and blot overlay analyses revealed that syndapin I binds the brain-specific proteins dynamin I, synaptojanin, and synapsin I via an SH3 domain-specific interaction. Coimmunoprecipitation of dynamin I with antibodies recognizing syndapin I and colocalization of syndapin I with dynamin I at vesicular structures in primary neurons indicate that syndapin I associates with dynamin I in vivo and may play a role in synaptic vesicle endocytosis. Furthermore, syndapin I associates with the neural Wiskott-Aldrich syndrome protein, an actin-depolymerizing protein that regulates cytoskeletal rearrangement. These characteristics of syndapin I suggest a molecular link between cytoskeletal dynamics and synaptic vesicle recycling in the nerve terminal.