3/12/2023 0 Comments Trim enabler oskar groth redditSubstrate specificity is conferred by the E3 enzyme, and several classes of E3 enzymes have been characterized. Protein ubiquitylation is carried out by three enzymes acting in sequence, termed E1, E2, and E3. When a chain of ubiquitins linked in series though ubiquitin Lysine 48 (K48-linked chains) are assembled, the ubiquitylated protein is targeted for destruction by the proteasome. Monoubiquitylation, the attachment of a single ubiquitin, can serve as a signal for endocytic sorting. Covalent attachment of the small protein ubiquitin to a target protein can alter the fate of the target protein in a number of ways ( Komander and Rape, 2012). Ring canals recruit a robust F-actin cytoskeleton and expand during oogenesis, reaching diameters greater than 10 μm.Īn important mechanism for regulating developmental events during gametogenesis is the ubiquitin-proteasome system (UPS). These components move to the oocyte through the ring canals, which must also grow to accommodate the flux of materials. Instead, the nurse cells become highly polyploid and synthesize mRNA, protein, and organelles that support oocyte growth. Over the course of several days, the oocyte grows in volume by five orders of magnitude without a substantial transcriptional contribution from the oocyte nucleus ( Cummings et al., 1971). The arrested cleavage furrows are subsequently transformed into stable intercellular bridges called ring canals through the recruitment of additional proteins ( Haglund et al., 2011). Cytokinesis does not complete during the mitotic divisions, leaving all 16 cells connected by the arrested cleavage furrows. One of these cells becomes the oocyte, while the remaining 15 differentiate as nurse cells. Oogenesis initiates at the anterior end of an ovariole, called the germarium, where a daughter of a germline stem cell undergoes four rounds of mitosis to generate a 16-cell cyst. This level of fecundity is achieved through mass production: the two Drosophila ovaries are made up of approximately 16 ovarioles, each of which contains a linear array of progressively developing eggs. Female fruit flies produce up to 60 eggs per day, each approximately 0.5 mm in length with a volume more than 1000-fold greater than that of a typical somatic cell. Many questions remain about how basic cell biological mechanisms are coordinated to achieve the remarkable form and function of animal gametes.ĭrosophila oogenesis provides a powerful model for investigating the specialized features of gamete development ( Bastock and St Johnston, 2008). The cell biology involved in gametogenesis is in many instances unusual: cells often develop in interconnected cysts, mature sperm have tails up to millimeters in length, oocytes can grow to macroscopic sizes, and the apoptotic machinery is used extensively both to promote waves of canonical apoptosis and also to coordinate non-apoptotic development and differentiation ( Arama et al., 2003 Peterson et al., 2015). Gamete formation in animals results in the production of the highly specialized cells responsible for species propagation, the sperm and egg ( Matova and Cooley, 2001 Roosen-Runge, 1969). These findings uncover an unusual mechanism during development wherein a specialized cytoskeletal structure is regulated and remodeled by the ubiquitin-proteasome system. Finally, we identify a short sequence motif in HtsRC that is necessary for Kelch binding. We present genetic evidence consistent with HtsRC being the CR元 Kelch substrate, as well as biochemical evidence indicating that HtsRC is ubiquitylated and degraded by the proteasome. CRISPR-mediated mutagenesis of HtsRC revealed its requirement in the recruitment of the ring canal F-actin cytoskeleton. Here, we use tandem affinity purification followed by mass spectrometry to identify HtsRC as the CR元 Kelch ring canal substrate. Previous work demonstrated that Kelch and Cullin 3 function together in a Cullin 3-RING ubiquitin ligase complex (CR元 Kelch) to organize the ring canal cytoskeleton, presumably by targeting a substrate for proteolysis. During Drosophila oogenesis, specialized actin-based structures called ring canals form and expand to accommodate growth of the oocyte.
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