Data Blitz Talks
Amy Scalera
(Rodal Lab)
A novel role of presynaptic periactive zone proteins in extracellular vesicle trafficking
Cells in the brain communicate with one another in multiple ways, electrically and chemically. Some cell-to-cell communication requires the use of cargo-carrying vesicles from one cell to the next. Ms. Scalera studies these vesicles in the fruit fly, exploring the question of what happens when they don’t perform as they should.
Extracellular vesicles (EVs) are small, endosomally-derived, membrane bound vesicles that can transport cargoes between cells, and are important for cell-cell communication in the nervous system. However, it remains unclear how specific endosomal cargoes are sorted for release through the EV pathway. Through a directed genetic screen, we identified an unexpected role for presynaptic periactive zone (PAZ) membrane remodeling proteins, which have canonical roles in clathrin-mediated endocytosis, in regulating the traffic of EV cargoes at the Drosophila NMJ. PAZ mutants exhibit a local and dramatic decrease in the levels of the EV cargoes Synaptotagmin-4 (Syt4) and Amyloid Precursor Protein (APP) at presynaptic terminals. Further, this decrease is sufficient to abolish Syt4 function and reduce APP toxicity, suggesting that loss of specific EV cargoes may play unrecognized roles in canonical phenotypes of PAZ mutants. Interestingly, this novel EV cargo traffic defect is genetically separable from the well-established functions of these proteins in synaptic vesicle recycling and synaptic growth.