RGD Reference Report - Capture of Dense Core Vesicles at Synapses by JNK-Dependent Phosphorylation of Synaptotagmin-4. - Rat Genome Database

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Capture of Dense Core Vesicles at Synapses by JNK-Dependent Phosphorylation of Synaptotagmin-4.

Authors: Bharat, Vinita  Siebrecht, Michael  Burk, Katja  Ahmed, Saheeb  Reissner, Carsten  Kohansal-Nodehi, Mahdokht  Steubler, Vicky  Zweckstetter, Markus  Ting, Jonathan T  Dean, Camin 
Citation: Bharat V, etal., Cell Rep. 2017 Nov 21;21(8):2118-2133. doi: 10.1016/j.celrep.2017.10.084.
RGD ID: 15023486
Pubmed: (View Article at PubMed) PMID:29166604
DOI: Full-text: DOI:10.1016/j.celrep.2017.10.084

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.

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Chga  (chromogranin A)
Kif1a  (kinesin family member 1A)
Mapk8  (mitogen-activated protein kinase 8)
Npy  (neuropeptide Y)
Syt4  (synaptotagmin 4)

Additional Information