KIF5B motor adaptor syntabulin maintains synaptic transmission in sympathetic neurons.

Authors: Ma, Huan  Cai, Qian  Lu, Wenbo  Sheng, Zu-Hang  Mochida, Sumiko 
Citation: Ma H, etal., J Neurosci. 2009 Oct 14;29(41):13019-29. doi: 10.1523/JNEUROSCI.2517-09.2009.
Pubmed: (View Article at PubMed) PMID:19828815
DOI: Full-text: DOI:10.1523/JNEUROSCI.2517-09.2009

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.

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CRRD ID: 13217418
Created: 2017-09-12
Species: All species
Last Modified: 2017-09-12
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.