Signaling pathways linking osmotic stress to adaptive responses: Roles for Rho family GTPases.
Published: 2006
Language: eng
Number of pages: 178
ISBN-13: 9780494219720
Description: Cell shrinkage is known to elicit three major adaptive responses: ion transport activation, gene transcription and cytoskeletal remodeling. Importantly, little is known about the signaling mechanisms linking the osmotic insult with these responses. Further, cytoskeletal remodeling in shrunken cells has not been fully characterized, and its potential role in sensing/transmitting to other adaptive responses is unclear. Since Rho family GTPases are known to be major organizers of F-actin, and since they have been linked to a variety of biochemical processes including ion transport and gene transcription, presumably via their effects on the cytoskeleton, we asked two general questions: (1) Are Rho GTPases sensitive to hyperosmotic stress? (2) Do Rho GTPases participate in signaling to the three major adaptive responses initiated by cell shrinkage? To answer these questions we first characterized the osmotic stress-induced F-actin remodeling. Our results indicated that cell shrinkage induces major changes in the F-actin cytoskeleton which manifests as an increase in  de novo F-actin polymerization at the cell periphery concomitant with an increase in myosin contractility. Importantly, our major findings indicated that Cdc42, Rac and Rho are each activated by hyperosmolarity and mediate the above mentioned changes in the cytoskeleton. Specifically, Cdc42 and Rac are involved in cortical F-actin polymerization via their effects on the actin related protein complex and cortactin localization, while the Rho-Rho kinase signaling pathway proved to be important for myosin light chain phosphorylation. Finally, in our cellular setting the activation of Rho GTPases and their subsequent effects on the cytoskeleton did not seem play a significant role in signaling to other adaptive responses including Na+-K +-2Cl- cotransporter mediated transport and osmotic response element promoter activity.
Notes: Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0036.

Thesis (Ph.D.)--University of Toronto, 2006.

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