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bioRxiv · 10.1101/172239

Ageing synaptic vesicles are inactivated by contamination with SNAP25

Truckenbrodt, S.·Viplav, A.·Jaehne, S.·Vogts, A.·Denker, A.·Wildhagen, H.·Fornasiero, E. F.·Rizzoli, S. O.
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Abstract

Old organelles can become a hazard to cellular function, by accumulating molecular damage. Mechanisms that identify aged organelles, and prevent them from participating in cellular reactions, are therefore necessary. We describe here one such mechanism for the synaptic vesicle recycling pathway. Using cultured hippocampal neurons, we found that newly synthesized vesicle proteins were incorporated in the active (recycling) pool, and were preferentially employed in neurotransmitter release. They remained in use for up to ~24 hours, during which they recycled up to a few hundred times. We could only detect one change in the molecular composition of the vesicles, an apparent accumulation of SNAP25 in the aged synaptic vesicles. Overexpression of SNAP25, both in wild-type form or in vesicle-bound form, inhibited exocytosis and promoted the co-localization of the vesicle molecules with a recycling endosome marker. This is in line with the hypothesis that the SNAP25 contamination causes the inactivation of the aged vesicles. The SNAP25 overexpression effect could be alleviated by co-expressing the vesicle-associated molecule CSP, which has been previously shown to be involved in chaperoning SNAP25 in the vesicle priming process. Overall, these results suggest that newly synthesized vesicle molecules are preferred in vesicle recycling, probably through a mechanism that renders their priming more efficient than that of aged vesicles.

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Truckenbrodt, S., Viplav, A., Jaehne, S., Vogts, A., Denker, A., Wildhagen, H., Fornasiero, E. F., Rizzoli, S. O.. 2017-08-03. Ageing synaptic vesicles are inactivated by contamination with SNAP25. https://doi.org/10.1101/172239

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