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  Capture of dense core vesicles at synapses by JNK-dependent phosphorylation of Synaptotagmin-4.

Bharat, V., Siebrecht, M., Burk, K., Ahmed, S., Reissner, C., Kohansal-Nodehi, M., et al. (2017). Capture of dense core vesicles at synapses by JNK-dependent phosphorylation of Synaptotagmin-4. Cell Reports, 21(8), 2118-2133. doi:10.1016/j.celrep.2017.10.084.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-55C3-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-1660-A
Genre: Journal Article

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Bharat, V., Author
Siebrecht, M., Author
Burk, K., Author
Ahmed, S., Author
Reissner, C., Author
Kohansal-Nodehi, M.1, Author              
Steubler, V., Author
Zweckstetter, M.2, Author              
Ting, J. T., Author
Dean, C., Author
Affiliations:
1Department of Neurobiology, MPI for Biophysical Chemistry, Max Planck Society, ou_578595              
2Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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 Abstract: Delivery of neurotrophins and neuropeptides via long-range trafficking of dense core vesicles (DCVs) from the cell soma to nerve terminals is essential for synapse modulation and circuit function. But the mechanism by which transiting DCVs are captured at specific sites is unknown. Here, we discovered that Synaptotagmin-4 (Syt4) regulates the capture and spatial distribution of DCVs in hippocampal neurons. We found that DCVs are highly mobile and undergo long-range translocation but switch directions only at the distal ends of axons, revealing a circular trafficking pattern. Phosphorylation of serine 135 of Syt4 by JNK steers DCV trafficking by destabilizing Syt4-Kif1A interaction, leading to a transition from microtubule-dependent DCV trafficking to capture at en passant presynaptic boutons by actin. Furthermore, neuronal activity increased DCV capture via JNK-dependent phosphorylation of the S135 site of Syt4. Our data reveal a mechanism that ensures rapid, site-specific delivery of DCVs to synapses.

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Language(s): eng - English
 Dates: 2017-11-21
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.celrep.2017.10.084
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Title: Cell Reports
Source Genre: Journal
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Pages: - Volume / Issue: 21 (8) Sequence Number: - Start / End Page: 2118 - 2133 Identifier: -