Characterizing a Novel Role for the Cytokinesis Scaffolding Protein Anillin in Regulating Cell-cell Junctions.

[摘要] Anillin is a highly conserved scaffolding protein required for successful cytokinesis in multiple biological organisms, from flies to human. During cytokinesis, Anillin helps to crosslink and stabilize a number of cytoskeletal, motor, and regulatory proteins including F-actin, Myosin II, Septins, the small GTPase RhoA, and its activity regulators MgcRacGAP and Ect2. Anillin scaffolds this network of proteins into a ring-like structure called the contractile ring just beneath the cell membrane at the cleavage furrow of dividing cells. The contractile ring provides the force to pinch one cell into two. Anillin’s localization has been well characterized in isolated cells where it is found in the nucleus of interphase cells, around the cell cortex during metaphase, at the equatorial cortex during anaphase, and at the cleavage furrow and midbody of dividing cells. Using the intact epithelium of Xenopus laevis embryos as a model system, my lab identified a population of Anillin localized at cell-cell junctions throughout the cell cycle. Characterizing the function of this novel junctional population of Anillin was the primary focus of this dissertation.Here, I show that Anillin is required for proper distribution of active RhoA at cell-cell junctions and for maintenance of a robust apical actomyosin belt, which is required for cell-cell junction integrity. I also characterize how Anillin is targeted to cell-cell junctions. I show that the Anillin Homology Domain (AHD) and Pleckstrin Homology (PH) Domain – regions of Anillin which mediate key interactions with RhoA, its activity regulators, lipids and septins – work cooperatively to target Anillin to junctions. Further, I investigate the importance and interdependence of an Anillin-Septin interaction for junctional recruitment of Anillin. Here, I show that Septins 2 and 7 are at cell-cell junctions, where Septin 2 closely co-localizes with Anillin. Additionally, I show that Septins have an important role in maintaining junction integrity, and may contribute to robust Anillin localization to cell-cell junctions. Taken together, this work characterizes a novel extra-mitotic role at cell-cell junctions for Anillin, which had previously been characterized only for its role in cytokinesis.

[发布机构] University of Michigan

[效力级别] Molecular

[关键词] Anillin and cell-cell junctions;Molecular;Cellular and Developmental Biology;Science;Cellular and Molecular Biology