Syntabulin is a microtubule-associated protein implicated in syntaxin transport in neurons.
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.
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.
Qingning
Q
Su
Qian
Q
Cai
Claudia
C
Gerwin
Carolyn L
CL
Smith
Zu-Hang
ZH
Sheng
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016547:Kinesins / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008868:Microtubule Proteins / Q000737:chemistry / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D050765:Qa-SNARE Proteins; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D050827:Syntaxin 1
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D050765:Qa-SNARE Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C494212:STX1A protein, human; C464570:SYBU protein, human; D050827:Syntaxin 1; D049452:Green Fluorescent Proteins; D016547:Kinesins