Circular oligomerization is an intrinsic property of synaptotagmin

• Autores: Wang, Jing; Li, Feng; Bello, Oscar Daniel; Sindelar, Charles Vaughn; Pincet, Frédéric; Krishnakumar, Shyam S.; Rothman, James E.
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: ELECTRON MICROSCOPY; MEMBRANE FUSION; NEUROSCIENCE; NEUROTRANSMITTERS
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Previously, we showed that synaptotagmin1 (Syt1) forms Ca2+-sensitive ring-like oligomers on membranes containing acidic lipids and proposed a potential role in regulating neurotransmitter release (Zanetti et al., 2016). Here, we report that Syt1 assembles into similar ring-like oligomers in solution when triggered by naturally occurring polyphosphates (PIP2 and ATP) and magnesium ions (Mg2+). These soluble Syt1 rings were observed by electron microscopy and independently demonstrated and quantified using fluorescence correlation spectroscopy. Oligomerization is triggered when polyphosphates bind to the polylysine patch in C2B domain and is stabilized by Mg2+, which neutralizes the Ca2+-binding aspartic acids that likely contribute to the C2B interface in the oligomer. Overall, our data show that ring-like polymerization is an intrinsic property of Syt1 with reasonable affinity that can be triggered by the vesicle docking C2B-PIP2 interaction and raise the possibility that Syt1 rings could pre-form on the synaptic vesicle to facilitate docking.
Fil: Wang, Jing. University of Yale. School of Medicine; Estados Unidos
Fil: Li, Feng. University of Yale. School of Medicine; Estados Unidos
Fil: Bello, Oscar Daniel. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Sindelar, Charles Vaughn. University of Yale. School of Medicine; Estados Unidos
Fil: Pincet, Frédéric. University of Yale. School of Medicine; Estados Unidos. Universite de Paris VI; Francia. Université Paris Diderot - Paris 7; Francia
Fil: Krishnakumar, Shyam S.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unidos
Fil: Rothman, James E.. University College London; Estados Unidos. University of Yale. School of Medicine; Estados Unidos