Barth Grant

Seminar Details

Host: Hays Rye

Time: 4:00 pm

Location: BCBP 108

Seminar Abstract

I will discuss two topics related to membrane tubule formation and severing, one in endosomes and one in lyososomes. In the endosomal pathway we recently gained new insights into the fundamental forces that drive the fission of recycling tubules and vesicles into recycling endosomes and free cargo carriers in the C. elegans intestine. Actin polymerization on endosomes has long been proposed to provide necessary membrane tension to promote fission, but a clear understanding of how actin contributes to tension, and how fission is regulated remain as large gaps in understanding. Our results provide surprising new evidence that non-muscle myosin II (NMII) functions with actin to regulate endocytic recycling. We further discovered a novel endosomal signaling hub centered on the Syndapin protein that regulates endosomal RhoA and NMII in this process, likely providing tension control during fission. In a second project we focused on the DNAJ-domain protein RME-8, first discovered in our C. elegans screens in non-neuronal tissues. Given recent human genetics studies linking human RME-8/DNAJC13 to Parkinsonism and Essential Tremor, we extended our RME-8 protein studies into neurons. We found that loss of RME-8/DNAJC13 in C. elegans and mouse neurons result in accumulation of grossly elongated autolysosomal tubules. In C. elegans we found that loss of RME-8 causes severe depletion of clathrin from neuronal autolysosomes, a phenotype shared with mutants affecting phosphatidylinositol-3-phosphate. We concluded that RME-8/DNAC13 plays a conserved but previously unrecognized role in autophagic lysosome reformation, likely affecting ALR tubule severing. This may explain RME-8 association with disease.