Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Synaptotagmin 1 oligomerization via the juxtamembrane linker regulates spontaneous and evoked neurotransmitter release Synaptotagmin-1 (syt1) is a Ca2+ sensor that regulates synaptic vesicle exocytosis. Cell-based experiments suggest that syt1 functions as a multimer, however biochemical and electron microscopy studies have yielded contradictory findings regarding putative self-association. Here, we performed dynamic light scattering on syt1 in solution, followed by electron microscopy, and used atomic force microscopy to study syt1 self-association on supported lipid bilayers under aqueous conditions. Ring-like multimers were clearly observed. Multimerization was enhanced by Ca2+ and required anionic phospholipids. Large ring-like structures ([~]180 nm) were reduced to smaller rings ([~]30 nm) upon neutralization of a cluster of juxtamembrane lysine residues; further substitution of residues in the second C2-domain completely abolished self-association. When expressed in neurons, syt1 mutants with graded reductions in self-association activity exhibited concomitant reductions in: a) clamping spontaneous release, and b) triggering and synchronizing evoked release. Thus, the juxtamembrane linker of syt1 plays a crucial role in exocytosis by mediating multimerization.
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The categories of this paper are: biochemistry
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The categories of this paper are: genetics
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The categories of this paper are: biology
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The categories of this paper are: developmental
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The categories of this paper are: education
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The categories of this paper are: cognition
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The categories of this paper are: cell
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The categories of this paper are: microbiology
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The categories of this paper are: communication
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The categories of this paper are: pharmacology
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The categories of this paper are: systems
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The categories of this paper are: ecology
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The categories of this paper are: molecular
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The categories of this paper are: epidemiology
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The categories of this paper are: paleontology
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The categories of this paper are: bioengineering