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Diverse roles of WAVE/SCAR complex polarizing epithelial cellular membranes during C.elegans development

by
Falshruti Patel
B.A., Rutgers University - 2004


Thesis Advisor: Martha Soto, Ph.D.
Graduate Program in Cellular & Developmental Biology

Life Sciences Building Auditorium
145 Bevier Road
Piscataway

Friday, August 3, 2012
12:00 noon


Abstract

Aberrant cell migration is one of the key features of metastatic cancer. Understanding the mechanisms that regulate normal cells migrate is of utmost importance to gain better insight into abnormal cancer cell migrations. For proper cell migration, the cells need to weaken existing cell adhesion with neighboring cells, migrate to new destination, and create and maintain new cell contacts with neighbors. The migrating epidermal cells of the model organism C.elegans are an attractive in vivo system to study the process of cell migration during embryonic morphogenesis. During morphogenesis the epidermal cells migrate as a sheet from the dorsal side of the embryo to the ventral midline in order to enclose the internal organs. We have identified a conserved branched actin promoting Rac-WAVE/SCAR-Arp2/3 pathway in C.elegans that regulates actin protrusion activity at the leading edge during epidermal migration. During morphogenesis the WAVE/SCAR-Arp2/3 pathway simultaneously regulates apical actin enrichment in another epithelial tissue, the intestine. In polarized intestinal epithelia, apical actin supports microvilli formation and apical junctions. We find that the WAVE/SCAR-based actin enrichment is dispensable for microvilli formation, but supports the apical actin belt. Arp2/3 induced actin polymerization regulates association of junctional proteins to the correct cellular membranes for apical junction maturation and maintenance. This suggests that WAVE/SCAR-Arp2/3 is required in maintenance of cell polarity through regulation of junctions. Since Arp2/3 based branched actin is proposed to have a role in trafficking of the junctional proteins, we investigated possible role of WAVE/SCAR-Arp2/3 pathway during endocytosis at the membrane. We find that WAVE/SCAR is the major regulator of branched actin nucleation during endocytosis at the cell membrane and is necessary for the formation of early endosomes. These studies demonstrate contributions of the WAVE/SCAR pathway-based actin nucleation to various cellular processes at the cell membranes during morphogenesis in polarized epithelial cells.


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