Academic journal article Genetics

Efficient Endocytic Uptake and Maturation in Drosophila Oocytes Requires Dynamitin/p50

Academic journal article Genetics

Efficient Endocytic Uptake and Maturation in Drosophila Oocytes Requires Dynamitin/p50

Article excerpt

MICROTUBULE motors such as cytoplasmic Dynein (hereafter referred to as Dynein) and proteins of the Kinesin superfamily play essential roles in cargo transport. Dynein is a minus-end motor and is responsible for the majority of minus-end transport within the cell (Kardon and Vale 2009). Mammalian genomes encode .40 different Kinesins, and most of these move cargo toward the plus-end of microtubules (Hirokawa et al. 2009). One type of cargo that is known to be transported by microtubule motors are vesicles of the endolysosomal system.

Cargoes that enter the cell via endocytosis follownumerous sorting pathways that ultimately determine their fate. For example, nutrient receptors such as the Transferrin receptor, are recycled back to the plasma membrane (Mayor et al. 1993; Huotari and Helenius 2011). Growth factor receptors and signaling molecules are often targeted for degradation (Beguinot et al. 1984; Huotari and Helenius 2011). This is necessary to attenuate growth-promoting signals. Persistent and uncontrolled growth-promoting signals are associated with cancer (Normanno et al. 2006). Cargoes that are destined for degradation transit through vesicles that undergo maturation from early endosome to late endosome. Late endosomes eventually fuse with acidic, degradative organelles known as lysosomes. Endocytic maturation involves the progressive and ordered association of specific factors with sorting vesicles (Huotari and Helenius 2011). Consequently, early endosomes are associated with a distinct set of proteins in comparison to late endosomes and lysosomes. However, endocytic maturation represents a continuum. Thus, vesicles of mixed identity can also be observed (Rink et al. 2005; Vonderheit and Helenius 2005).

Studies in mammalian cell lines have demonstrated a role for Dynein in motility of early and late endosomes (Valetti et al. 1999; Jordens et al. 2001; Driskell et al. 2007; Flores-Rodriguez et al. 2011). Sorting of epidermal growth factor receptor (EGFR) from internalized Transferrin also appears to require Dynein (Driskell et al. 2007). However, whether Dynein is actually required for endosome maturation is unknown. Some studies have hinted at such a role. For example, depletion of Dynein light intermediate chains resulted in enlarged late endosomes (Tan et al. 2011). The rate at which EGFR was degraded was also reduced in these cells (Tan et al. 2011). In a separate study in which early endosomes were artificially enlarged, Dynein was shown to be required for tubule formation after fusion of early endosomes (Skjeldal et al. 2012). The implication of this finding is that Dynein might be involved in sorting cargo within early endosomes during their maturation into late endosomes (Skjeldal et al. 2012).

In this study, we used the Drosophila oocyte as a model to examine the role of Dynein in endocytic maturation. The Drosophila egg chamber contains 16 germline cells surrounded by a layer of somatic cells known as follicle cells. One of the 16 germline cells differentiates to become the oocyte, and the remaining 15 become nurse cells (Spradling 1994). During vitellogenic stages of egg chamber maturation (stages 8-10), there is a tremendous up-regulation of clathrin-mediated endocytosis within the oocyte. During these stages, Yolk proteins bind to the vitellogenin receptor, Yolkless (Yl). After endocytosis, Yl is recycled back to the plasma membrane, whereas Yolk proteins are trafficked through the endocytic pathway and stored in condensed yolk granules (DiMario and Mahowald 1987; Tsuruhara et al. 1990; Schonbaum et al. 2000). Yolk granules are the functional equivalent of dormant lysosomes and represent the endproduct of Yolk protein endocytosis. The granules serve as a food source for the developing embryo. Thus, a defect in endocytic maturation will be reflected by a loss or reduction in the number of condensed yolk granules, a scenario that has been demonstrated using rab5 nulls (Compagnon et al. 2009). …

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