Dynamin proline-rich domain isoform abundance, not identity, determines synaptic vesicle recycling efficiency in Drosophila

Silveira, A. M.; De Leon Gonzalez, K. M.; Scalera, A. L.; Westhoff, L. J.; Roytman, K. A.; Del Signore, S. J.; Goode, B. L.; Rodal, A. A.

doi:10.64898/2026.08.24.746809

bioRxiv · 10.64898/2026.08.24.746809

Dynamin proline-rich domain isoform abundance, not identity, determines synaptic vesicle recycling efficiency in Drosophila

Silveira, A. M.·De Leon Gonzalez, K. M.·Scalera, A. L.·Westhoff, L. J.·Roytman, K. A.·Del Signore, S. J.·Goode, B. L.·Rodal, A. A.

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Abstract

During neurotransmission, synaptic vesicle exocytosis adds membrane and proteins to the cell surface. To sustain further release, this material must be retrieved, via several distinct endocytic modes matched to the level of exocytosis. The GTPase dynamin plays a central role in endocytosis, but it has remained unclear which endocytic modes it supports. In mammals, distinct dynamin gene products with different proline-rich domains (PRDs) are proposed to mediate particular modes of endocytosis; however, the function of each PRD isoform has not been tested in an organism. Drosophila dynamin is encoded by one gene (shibire) that produces long and short PRD isoforms (Shi-L and Shi-S), which differ by a 48 amino acid C-terminal extension. Using isoform-specific knockin and knockdown tools, we found that loss of the more abundant Shi-S isoform disrupted bulk endocytosis and vesicle reformation under high exocytic demand, reduced evoked transmission at moderate levels of activity, and enhanced spontaneous release at rest. These functions did not depend on the PRD extension, as either isoform could rescue these phenotypes when re-expressed. Our results indicate that dynamin contributes to vesicle recycling across multiple endocytic retrieval modes and that PRD specialization is not required for these functions.

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Silveira, A. M., De Leon Gonzalez, K. M., Scalera, A. L., Westhoff, L. J., Roytman, K. A., Del Signore, S. J., Goode, B. L., Rodal, A. A.. 2026-08-25. Dynamin proline-rich domain isoform abundance, not identity, determines synaptic vesicle recycling efficiency in Drosophila. https://doi.org/10.64898/2026.08.24.746809

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