Capture of dense core vesicles at synapses by JNK-dependent phosphorylation of Synaptotagmin-4
| Autor: | Vinita Bharat, Michael Siebrecht, Katja Burk, Saheeb Ahmed, Carsten Reissner, Mahdokht Kohansal-Nodehi, Vicky Steubler, Markus Zweckstetter, Jonathan T. Ting, Camin Dean |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
MAP Kinase Signaling System
metabolism [Microtubules] metabolism [Neuropeptides] Presynaptic Terminals metabolism [Axons] Microtubules Article metabolism [Synaptotagmins] Syt4 protein rat Synaptotagmins Animals metabolism [Secretory Vesicles] metabolism [Nerve Endings] ddc:610 Phosphorylation Rats Wistar lcsh:QH301-705.5 physiology [MAP Kinase Signaling System] Nerve Endings Neurons Secretory Vesicles Neuropeptides Axons Drosophila melanogaster lcsh:Biology (General) nervous system metabolism [Neurons] metabolism [Presynaptic Terminals] |
| Zdroj: | Cell Reports Cell reports 21(8), 2118-2133 (2017). doi:10.1016/j.celrep.2017.10.084 Cell Reports, Vol 21, Iss 8, Pp 2118-2133 (2017) |
| Popis: | Summary 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. Graphical Abstract Highlights • Syt4-bearing dense core vesicles in axons traffic continually in a circular pattern • Phosphorylation of S135 of Syt4 by JNK destabilizes Syt4-Kif1A binding • Destabilized Syt4-Kif1A binding promotes capture of vesicles at synapses by actin • Neuronal activity increases vesicle capture via S135-dependent JNK phosphorylation Bharat et al. show that Synaptotagmin-4 (Syt4) on highly mobile dense core vesicles (DCVs) in axons binds the motor protein Kif1A. Phosphorylation of the S135 site of Syt4 by JNK destabilizes Syt4-Kif1A binding, leading to capture of DCVs at synapses by actin. Neuronal activity increases capture via this mechanism. |
| Databáze: | OpenAIRE |
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