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Pathak, M.

Publications and source records attributed to Pathak, M..

2 recordsLinked to original sources

Mouse pre-meiotic germline cysts contain fusome-like structure dependent on Dazl that mediates cyst fragmentation and oocyte development

Mouse female primordial germ cells (PGCs) undergo five synchronous, incomplete mitotic divisions, and send each resulting germline cyst into meiosis to fragment and produce 4-6 oocytes and 24-26 supportive nurse cells. However, no system of polarity has been found to specify mammalian oocytes, link them appropriately to nurse cells and enable them to acquire high quality organelles and cytoplasm. We report that mouse cysts develop an asymmetric Golgi, endoplasmic reticulum (ER) and microtubule-associated "fusome", similar to the oocyte-determining fusome in Drosophila cysts. The mouse fusome distributes asymmetrically among cyst cells and enriches in future oocytes with Pard3, and Golgi-endosomal UPR (unfolded protein response) proteins. Spindle remnants rich in stable acetylated microtubules, like those building the Drosophila and Xenopus fusomes, transiently link early mouse cyst cells for part of each cell cycle. A non-random gap in these microtubules predicts that initial cysts fragment into similar six-cell derivatives, providing a potential mechanism for producing uniform oocytes. Together with previous studies these results argue that a polarized fusome underlies the development of female gametes from the PGC to follicular oocyte stages in diverse animals including mammals.

developmental biology↗

Wisteria floribunda agglutinin enhances Zaire ebolavirus entry through interactions at specific N-linked glycosylation sites on the virus glycoprotein complex

Entry of Zaire ebolavirus (EBOV) into a host cell is a complex process requiring interactions between the viral glycoproteins (GP) and cellular factors. These entry factors are cell-specific and can include cell surface lectins and phosphatidylserine receptors. NPC1 is critical to the late stage of the entry process. Entry has been demonstrated to be enhanced by interactions between the virion and surface-expressed lectins, which interact with carbohydrate moieties attached to the GP. In addition, soluble lectins, including mannose binding lectin (MBL), can enhance entry in vitro. However, the mechanism of lectin-mediated enhancement remains to be defined. This study investigated the potential of three plant lectins, Wisteria floribunda agglutinin (WFA), soybean agglutinin (SBA) and Galanthus nivalis agglutinin (GNA), which possess different carbohydrate binding specificities, to enhance EBOV entry by binding to the GP. WFA was observed to potently enhance entry of lentiviral pseudotype viruses (PVs) expressing the GP of three Ebolavirus species (Zaire, Sudan [SUDV] and Reston [RESTV]), with the greatest impact on EBOV. SBA had a modest enhancing effect on entry that was specific to EBOV, while GNA had no impact on entry of any of the Ebolavirus species. None of the lectins enhanced entry of control PVs expressing the surface proteins of other RNA viruses tested. WFA was demonstrated to bind directly with the EBOV-GP via the glycans, and mutational analysis implicated N238 as contributing to the interaction. Furthermore, enhancement was observed in both human and bat cell lines indicating a highly conserved mechanism of action. We conclude that binding of WFA to EBOV GP through interactions including the glycan at N238 results in GP alterations that enhance entry, providing evidence of a mechanism for lectin-mediated virus entry enhancement. Targeting lectin-ligand interactions presents a potential strategy for restricting Ebolavirus entry.

microbiology↗