1
Synaptic Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 3B203, MSC 3701, 35 Convent Drive, Bethesda, MD 20892-3701, USA.
2
Light Imaging Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 3B203, MSC 3701, 35 Convent Drive, Bethesda, MD 20892-3701, USA.
3
Laboratory of Neurobiology, Shanghai Second Medical University, 280 Chong Qing Nan Road, 200025, Shanghai, China.
Different types of cargo vesicles containing presynaptic proteins are transported from the nerve cell body to the nerve terminal, and participate in the formation of active zones. However, the identity of the membranous cargoes and the nature of the motor−cargo interactions remain unsolved. Here, we report the identification of a syntaxin-1-binding protein named syntabulin. Syntabulin attaches syntaxin-containing vesicles to microtubules and migrates with syntaxin within the processes of hippocampal neurons. Knock-down of syntabulin expression with targeted small interfering RNAs (siRNAs) or interference with the syntabulin−syntaxin interaction inhibit attachment of syntaxin-cargo vesicles to microtubules and reduce syntaxin-1 distribution in neuronal processes. Furthermore, conventional kinesin I heavy chain binds to syntabulin and associates with syntabulin-linked syntaxin vesicles in vivo. These findings suggest that syntabulin functions as a linker molecule that attaches syntaxin-cargo vesicles to kinesin I, enabling the transport of syntaxin-1 to neuronal processes.
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