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Biology subjects

Abdu, Y.

Publications and source records attributed to Abdu, Y..

3 recordsLinked to original sources

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

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.

cell biology↗

ZIF-1-mediated degradation of endogenous and heterologous zinc finger proteins in the C. elegans germ line

Rapid and conditional protein depletion is the gold standard genetic tool for deciphering the molecular basis of developmental processes. Previously, we showed that by conditionally expressing the E3 ligase substrate adaptor ZIF-1 in Caenorhabditis elegans somatic cells, proteins tagged with the first CCCH Zn finger (ZF1) domain from the germline regulator PIE-1 degrade rapidly, resulting in loss-of-function phenotypes. The described role of ZIF-1 is to clear PIE-1 and several other CCCH Zn finger proteins from early somatic cells, helping to enrich them in germline precursor cells. Here, we show that proteins tagged with the PIE-1 ZF1 domain are subsequently cleared from primordial germ cells in embryos and from undifferentiated germ cells in larvae and adults by ZIF-1. We harness germline ZIF-1 activity to degrade a ZF1-tagged heterologous protein from PGCs and show that its depletion produces phenotypes equivalent to those of a null mutation. Our findings reveal that ZIF-1 switches roles from degrading CCCH Zn finger proteins in somatic cells to clearing them from undifferentiated germ cells, and that ZIF-1 activity can be harnessed as a new genetic tool to study the early germ line.

cell biology↗

Independent regulation of mtDNA quantity and quality resets the mitochondrial genome in C. elegans primordial germ cells

Mitochondria contain an independent genome, called mtDNA, which contains essential metabolic genes. Although mtDNA mutations occur at high frequency, they are inherited infrequently, indicating that germline mechanisms limit their accumulation. To determine how germline mtDNA is regulated, we examined the control of mtDNA quantity and quality in C. elegans primordial germ cells (PGCs). We show that PGCs generate a bottleneck in mtDNA number by segregating mitochondria into lobe-like protrusions that are cannibalized by adjacent cells, reducing mtDNA content two-fold. As PGCs exit quiescence and divide, mtDNAs replicate to maintain a set point of [~]200 mtDNAs per germline stem cell. Whereas PGC lobe cannibalism eliminates mtDNAs stochastically, we show that the kinase PINK1, operating independently of Parkin and autophagy, preferentially reduces the fraction of mutant mtDNAs. Thus, PGCs employ parallel mechanisms to control both the quantity and quality of the founding population of germline mtDNAs.

cell biology↗