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Syntabulin is a microtubule-associated protein implicated in syntaxin transport in neurons

Nature Cell Biology volume 6, pages 941–953 (2004)Cite this article

Abstract

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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Figure 1: Syntabulin is a microtubule-associated protein in neuronal somata and processes.
Figure 2: DsRed–syntaxin vesicles align with EGFP–syntabulin in COS cells.
Figure 3: DsRed–syntaxin vesicles co-localize with syntabulin and Bassoon and migrate along the neuronal processes.
Figure 4: The syntaxin-binding domain competes with syntabulin for binding to syntaxin.
Figure 5: The SBD blocks the attachment of syntaxin-containing structures to syntabulin.
Figure 6: Overexpression of the syntaxin-binding domain reduces syntaxin-1 distribution in neuronal processes.
Figure 7: siRNA knocks down syntabulin expression and reduces distribution of endogenous syntaxin-1 in neuronal processes.
Figure 8: Conventional kinesin I drives the transport of the syntabulin-linked membrane organelles.

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GenBank/EMBL/DDBJ

Data deposits

  • The GenBank accession number for the syntabulin sequence reported in this paper is AY705385.

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Acknowledgements

We thank the following people for their help: K. J. Swartz, C. Blackstone and C. T. Yokoyama for their critical reading of the manuscript; P. De Camilli, J. Lippincott-Schwartz and members of the Sheng laboratory for discussion; L. S. Goldstein for GST–KLC constructs and R. J. Diefenbach for His–KHC DNAs; M. Takahashi for SNARE antibodies; J. W. Nagle for DNA sequencing; S. Cheng for her assistance in EM examination; and J. Kang for image analysis. This work was supported by intramural research program of NINDS, NIH (Z.-H.S.). Q.C. is a graduate student of the NIH-SSMU (Shanghai Second Medical University) Joint Ph.D. Program in Neuroscience partially supported by the Shanghai Science Technology Development Foundation (01JC4023). We acknowledge P.-H. Lu for her support to the joint NIH-SSMU training program.

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  1. Qingning Su and Qian Cai: These authors contributed equally to this work.

Authors and Affiliations

  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, 20892-3701, MD, USA

    Qingning Su, Qian Cai, Claudia Gerwin & Zu-Hang Sheng

  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, 20892-3701, MD, USA

    Carolyn L. Smith

  3. Laboratory of Neurobiology, Shanghai Second Medical University, 280 Chong Qing Nan Road, Shanghai, 200025, China

    Qian Cai

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Correspondence to Zu-Hang Sheng.

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Su, Q., Cai, Q., Gerwin, C. et al. Syntabulin is a microtubule-associated protein implicated in syntaxin transport in neurons. Nat Cell Biol 6, 941–953 (2004). https://doi.org/10.1038/ncb1169

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