Show simple item record

dc.contributor.advisor Soderling, Scott H en_US
dc.contributor.author Mason, Frank Marshall en_US
dc.date.accessioned 2012-05-29T16:40:31Z
dc.date.issued 2011 en_US
dc.identifier.uri http://hdl.handle.net/10161/5644
dc.description Dissertation en_US
dc.description.abstract <p>Essential and diverse biological processes such as cell division, morphogenesis and migration are regulated by a family of molecular switches called Rho GTPases. These proteins cycle between active, GTP-bound states and inactive, GDP-bound state and this cycle is regulated by families of proteins called Rho GEFs and GAPs. GAPs are proteins that stimulate the intrinsic GTPase activity of Rho-family proteins, potentiating the active to inactive transition. GAPs target specific spatiotemporal pools of GTPases by responding to cellular cues and utilizing protein-protein interactions. By dissecting these interactions and pathways, we can infer and then decipher the biological functions of these GAPs.</p><p>This work focuses on the characterization of a novel Rho-family GAP called srGAP2. In this study, we identify that srGAP2 is a Rac-specific GAP that binds a Formin-family member, Formin-like 1 (FMNL1). FMNL1 is activated by Rac and polymerizes, bundles and severs actin filaments. srGAP2 specifically inhibits the actin severing of active FMNL1, and the assembly of an srGAP2-FMNL1 complex is regulated by Rac. Work on FMNL1 shows that it plays important roles in regulating phagocytosis and adhesion in macrophages. To learn more about srGAP2 and its role in regulating FMNL1, we studied macrophages isolated from an srGAP2 KO mouse we have recently generated. This has proven quite fruitful: loss of srGAP2 decreases the ability for macrophages to invade through extracellular matrix but increases phagocytosis. These results suggest that these two processes might be coordinated in vivo by srGAP2 and that srGAP2 might be a critical regulator of the innate immune system.</p> en_US
dc.subject Cellular Biology en_US
dc.subject Actin en_US
dc.subject Cdc42 en_US
dc.subject Formin en_US
dc.subject Macrophage en_US
dc.subject Rac en_US
dc.subject Rho en_US
dc.title Identification of a Novel Formin-GAP Complex and Its Role in Macrophage Migration and Phagocytosis en_US
dc.type Dissertation en_US
dc.department Cell Biology en_US
duke.embargo.months 24 en_US
duke.embargo.release 2014-05-19

Files in this item

This item appears in the following Collection(s)

Show simple item record