Research article summary (published 12 Oct 2009):

KIF5B motor adaptor syntabulin maintains synaptic transmission in sympathetic neurons.

Full Abstract

Newly synthesized synaptic proteins and mitochondria are transported along lengthy neuronal processes to assist in the proper assembly of developing synapses and activity-dependent remodeling of mature synapses. Neuronal transport is mediated by motor proteins that associate with their cargoes via adaptors and travel along the cytoskeleton within neuronal processes. Our previous studies in developing hippocampal neurons revealed that syntabulin acts as a KIF5B motor adaptor and mediates anterograde transport of presynaptic cargoes and mitochondria, presynaptic assembly, and activity-induced plasticity. Here, using cultured superior cervical ganglion neurons combined with manipulation of syntabulin expression or interference with its interaction with KIF5B, we uncover a crucial role for syntabulin in the maintenance of presynaptic function. Syntabulin loss-of-function delayed the appearance of synaptic activity in developing neurons and impaired synaptic transmission in mature neurons, including reduced basal activity, accelerated synaptic depression under high-frequency firing, slowed recovery rates after synaptic vesicle depletion, and impaired presynaptic short-term plasticity. These defects correlated with reduced mitochondrial distribution along neuronal processes and were rescued by the application of ATP within presynaptic neurons. These results suggest that syntabulin supports the axonal transport of mitochondria and concomitant ATP production at presynaptic terminals. ATP supply from locally stationed mitochondria is in turn necessary for the efficient mobilization of synaptic vesicles into the readily releasable pool. These findings emphasize the critical role of KIF5B-syntabulin-mediated axonal transport in the maintenance of presynaptic function and regulation of synaptic plasticity.

Author information

Author/s: Ma, Huan (H); Cai, Qian (Q); Lu, Wenbo (W); Sheng, Zu-Hang (ZH); Mochida, Sumiko (S);

Affiliation: Department of Physiology, Tokyo Medical University, Tokyo 160-8402, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 29 (issue 41) : pp 13019-29

Dates: Created 2009/10/15; Completed 2009/10/30;

PMID: 19828815, status: MEDLINE (last retrieval date: 10/30/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Action Potentials - genetics; physiology Adenosine Triphosphate - pharmacology Animals Animals, Newborn Biophysical Phenomena - drug effects; genetics Cells, Cultured Dose-Response Relationship, Drug Electric Stimulation - methods Excitatory Postsynaptic Potentials - physiology Green Fluorescent Proteins - genetics Kinesin - genetics; metabolism Luminescent Proteins - genetics; metabolism Membrane Proteins - genetics; metabolism Mitochondria - metabolism

Mutation - genetics Neuronal Plasticity - drug effects; genetics; physiology Patch-Clamp Techniques Protein Transport - genetics RNA, Small Interfering - genetics; metabolism Rats Rats, Wistar Sensory Receptor Cells - physiology; ultrastructure Sucrose - pharmacology Superior Cervical Ganglion - cytology Sweetening Agents - pharmacology Synaptic Transmission - drug effects; genetics; physiology Time Factors Transfection - methods

Associated Chemicals: KIF5B protein, rat (0) ; Luminescent Proteins (0) ; Membrane Proteins (0) ; RNA, Small Interfering (0) ; Sweetening Agents (0) ; fluorescent protein 583 (0) ; syntabulin protein, rat (0) ; Green Fluorescent Proteins (147336-22-9) ; Adenosine Triphosphate (56-65-5) ; Sucrose (57-50-1) ; Kinesin (EC 3.6.1.-)

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