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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 (PIP 2 ), 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.
Insights
This study reveals RAB-35 as a key regulator of trogocytosis, a cellular cannibalism process. RAB-35 controls both the "biting" cell
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Trogocytosis is a cellular process where one cell consumes parts of another.
- Understanding the molecular mechanisms of trogocytosis is crucial for developmental processes.
- A specific trogocytosis event occurs in *C. elegans* involving endodermal cells and primordial germ cells (PGCs).
Purpose of the Study:
- To investigate the molecular mechanisms underlying a programmed trogocytosis event in *C. elegans*.
- To identify key regulators of this specific cellular cannibalism process.
- To elucidate the distinct roles of identified regulators in both the 'biting' and 'bitten' cells.
Main Methods:
- Conducted a genetic screen in *C. elegans* to identify genes involved in trogocytosis.
- Utilized molecular and cellular biology techniques to analyze the function of identified genes.
- Investigated the localization and function of RAB-35 in both endodermal and PGCs.
Main Results:
- Identified the Rab family GTPase *rab-35* as a central regulator of trogocytosis.
- RAB-35 functions in both the endodermal (biting) and PGC (bitten) cells.
- In endodermal cells, RAB-35 promotes PGC lobe digestion by removing PIP2.
- In PGCs, RAB-35 works with the ESCRT complex to facilitate lobe scission.
Conclusions:
- Discovered RAB-35 as a novel regulator of trogocytosis with dual roles in distinct cell types.
- Demonstrated that the 'bitten' cell actively participates in the scission of its own membrane fragments.
- Provided new insights into the complex molecular machinery governing cellular cannibalism during development.
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