TY - JOUR

T1 - An endocytic scaffolding protein together with Synapsin regulates synaptic vesicle clustering in the drosophila neuromuscular junction

AU - Winther, Åsa M.E.

AU - Vorontsova, Olga

AU - Rees, Kathryn A.

AU - Näreoja, Tuomas

AU - Sopova, Elena

AU - Jiao, Wei

AU - Shupliakov, Oleg

N1 - Conference code: 31

PY - 2015/11/4

Y1 - 2015/11/4

N2 - Many endocytic proteins accumulate in the reserve pool of synaptic vesicles (SVs) in synapses and relocalize to the endocytic periactive zone during neurotransmitter release. Currently little is known about their functions outside the periactive zone. Here we show that in the Drosophila neuromuscular junction (NMJ), the endocytic scaffolding protein Dap160 colocalizes during the SV cycle and forms a functional complex with the SV-associated phosphoprotein synapsin, previously implicated in SV clustering. This direct interaction is strongly enhanced under phosphorylation-promoting conditions and is essential for proper localization of synapsin at NMJs. In a dap160 rescue mutant lacking the interaction between Dap160 and synapsin, perturbed reclustering of SVs during synaptic activity is observed. Our data indicate that in addition to the function in endocytosis, Dap160 is a component of a network of protein-protein interactions that serves for clustering of SVs in conjunction with synapsin. During the SV cycle, Dap160 interacts with synapsin dispersed from SVs and helps direct synapsin back to vesicles. The proteins function in synergy to achieve efficient clustering of SVs in the reserve pool.

AB - Many endocytic proteins accumulate in the reserve pool of synaptic vesicles (SVs) in synapses and relocalize to the endocytic periactive zone during neurotransmitter release. Currently little is known about their functions outside the periactive zone. Here we show that in the Drosophila neuromuscular junction (NMJ), the endocytic scaffolding protein Dap160 colocalizes during the SV cycle and forms a functional complex with the SV-associated phosphoprotein synapsin, previously implicated in SV clustering. This direct interaction is strongly enhanced under phosphorylation-promoting conditions and is essential for proper localization of synapsin at NMJs. In a dap160 rescue mutant lacking the interaction between Dap160 and synapsin, perturbed reclustering of SVs during synaptic activity is observed. Our data indicate that in addition to the function in endocytosis, Dap160 is a component of a network of protein-protein interactions that serves for clustering of SVs in conjunction with synapsin. During the SV cycle, Dap160 interacts with synapsin dispersed from SVs and helps direct synapsin back to vesicles. The proteins function in synergy to achieve efficient clustering of SVs in the reserve pool.

KW - Drosophila neuromuscular junction

KW - Scaffolding proteins

KW - Synapse

KW - Synapsin

KW - Synaptic vesicles

KW - Vesicle clustering

UR - http://www.scopus.com/inward/record.url?scp=84946426418&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1675-15.2015

DO - 10.1523/JNEUROSCI.1675-15.2015

M3 - Article

C2 - 26538647

AN - SCOPUS:84946426418

VL - 35

SP - 14756

EP - 14770

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 44

T2 - 31st Congress of the European-College-of-Neuropsychopharmacology (ECNP)

Y2 - 6 October 2018 through 9 October 2018

ER -