The N-Terminal DH-PH Domain of Trio Induces Cell Spreading and Migration by Regulating Lamellipodia Dynamics in a Rac1-Dependent Fashion

The guanine-nucleotide exchange factor Trio encodes two DH-PH domains that catalyze nucleotide exchange on Rac1, RhoG and RhoA. The N-terminal DH-PH domain is known to activate Rac1 and RhoG, whereas the C-terminal DH-PH domain can activate RhoA. The current study shows that the N-terminal DH-PH domain, upon expression in HeLa cells, activates Rac1 and RhoG independently from each other. In addition, we show that the flanking SH3 domain binds to the proline-rich region of the C-terminus of Rac1, but not of RhoG. However, this SH3 domain is not required for Rac1 or RhoG GDP-GTP exchange. Rescue experiments in Trio-shRNA-expressing cells showed that the N-terminal DH-PH domain of Trio, but not the C-terminal DH-PH domain, restored fibronectin-mediated cell spreading and migration defects that are observed in Trio-silenced cells. Kymograph analysis revealed that the N-terminal DH-PH domain, independent of its SH3 domain, controls the dynamics of lamellipodia. Using siRNA against Rac1 or RhoG, we found that Trio-D1-induced lamellipodia formation required Rac1 but not RhoG expression. Together, we conclude that the GEF Trio is responsible for lamellipodia formation through its N-terminal DH-PH domain in a Rac1-dependent manner during fibronectin-mediated spreading and migration

Genitourinary Pathology (Including Adrenal Gland)

Our aims in constructing the Genitourinary Pathology chapter are to describe neoplasms of the adrenal gland, urothelial tract, kidney, penis, prostate, and testis in a manner that is both useful for the practicing surgical pathologist and that may be used as a reference for all students of urologic pathology. Whereas the text and figures describe the salient morphologic, immunohistochemical, and molecular attributes for each tumor type and encompass the latest classification schemes, the narrative integrates the clinical and pathological findings that are commonly encountered during surgical pathology sign-out of these cases. Accordingly, it is our hope that this chapter will serve as a guide for both general and subspecialized pathologists in contemporary practice