RAB-35 regulates distinct steps of trogocytosis in the biting and bitten cell

Abstract

Trogocytosis is a form of cellular cannibalism in which a cell "bites" off pieces of another cell. Here, we investigate the molecular mechanisms of a developmentally programmed C. elegans trogocytic event that occurs when endodermal cells bite off and digest pieces of primordial germ cells (PGCs) called lobes. Through a genetic screen, we identify the Rab family small GTPase rab-35 as a central regulator of trogocytosis and show that its function is required in both biting (endodermal) and bitten (PGC) cells. Within endodermal cells, RAB-35 enriches around trogocytosed PGC lobes, promotes the removal of phosphatidylinositol 4,5-bisphosphate (PIP2), and is required for lobe digestion. By contrast, we show that RAB-35 within PGCs works with the ESCRT complex to promote scission of the PGC lobe from the cell body. Our findings identify a new regulator of trogocytosis that has distinct functions in the biting and bitten cells and provide evidence that the bitten cell contributes to the scission of its own membrane.