Snapin facilitates the synchronization of synaptic vesicle fusion.
Synaptic vesicle (SV) fusion is a fine-tuned process requiring a concert of fusion machineries. Using cortical neurons from snapin-deficient mice, we reveal a role for Snapin in facilitating synchronous release. In addition to reduced frequency of miniature excitatory postsynaptic currents (mini-EPSCs) and smaller release-ready vesicle pool (RRP) size, snapin deficiency results in EPSCs with multiple peaks and increased rise and decay times, reflecting "desynchronized" SV fusion. These defects impair both synaptic precision and efficacy during sustained neurotransmission. Transient expression of Snapin not only rescues the slowed kinetics of EPSCs, but also further accelerates the rate found in wild-type neurons. Furthermore, expression of Snapin-C66A, a dimerization-defective mutant with impaired interactions with SNAP-25 and Synaptotagmin, reduces the RRP size but exhibits less effect on synchronized fusion. Our studies provide mechanistic insights into a dual role of Snapin in enhancing the efficacy of SV priming and in fine-tuning synchronous SV fusion.
Pan
Ping-Yue
PY
Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 3B203, 35 Convent Drive, Bethesda, MD 20892-3701, USA.
Tian
Jin-Hua
JH
Sheng
Zu-Hang
ZH
D000818:Animals; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics*; D008561:Membrane Fusion / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics / Q000378:metabolism; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
C498451:Snapin protein, mouse; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins; D050857:Synaptotagmins