Limited intermixing of synaptic vesicle components upon vesicle recycling.
Traffic. 2010 Jun; 11(6):800-12
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This paper is very interesting as it provides strong support to the 'protein clustering model' of synaptic vesicle recycling.
After a synaptic vesicle has collapsed into the plasma membrane, it is recaptured by clathrin-mediated endocytosis in the periactive zone. A major question to resolve is how a novel vesicle with similar content as the previously fused vesicle can form. One model implies that a pool of vesicle proteins reside in the plasma membrane. Following fusion, the proteins of a vesicle mix with this pool and, subsequently, a new set of vesicle proteins are gathered in a sorting process. An alternative model implies that the proteins of a vesicle remain clustered after fusion. The subsequent endocytic process would then be simpler and less dependent on protein sorting. Opazo et al. now show that endogenous synaptotagmin (monitored by intraluminal domain antibodies) does not diffuse away from synapses into adjacent axonal segments during physiological stimulation conditions. Such diffusion, an argument for the first model above, has previously been observed with expressed pH-sensitive green fluorescent protein (pHluorin)-tagged vesicle proteins. Second, they found that little or no mixing of synaptotagmin occurred when different pools were labeled sequentially with different fluorophores. Third, they found that endogenous synaptic vesicle proteins have a clustered distribution in the plasma membrane whereas expressed synaptopHluorin-tagged proteins have a diffuse distribution.
The paper thus supports the model implying that vesicle proteins remain clustered after exocytosis. As pointed out by the authors, however, it is not possible to conclude whether clusters contain the full complement of a vesicle's proteins or whether they contain smaller fractions. The study also emphasizes that results obtained with expressed tagged vesicle proteins need to be interpreted with caution.
Brodin L: F1000Prime Recommendation of [Opazo F et al., Traffic 2010, 11(6):800-12]. In F1000Prime, 26 Mar 2010; DOI: 10.3410/f.2681956.2344054. F1000Prime.com/2681956#eval2344054
F1000Prime Recommendations, Dissents and Comments for [Opazo F et al., Traffic 2010, 11(6):800-12]. In F1000Prime, 19 Apr 2014; F1000Prime.com/2681956
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