Rab6 regulates cell migration and invasion by recruiting Cdc42 and modulating its activity.

Rab6 regulates cell migration and invasion by recruiting Cdc42 and modulating its activity.
Cell Mol Life Sci. 2019 Mar 04;:
Authors: Vestre K, Kjos I, Guadagno NA, Borg Distefano M, Kohler F, Fenaroli F, Bakke O, Progida C
Abstract
Rab proteins are master regulators of intracellular membrane trafficking, but they also contribute to cell division, signaling, polarization, and migration. The majority of the works describing the mechanisms used by Rab proteins to regulate cell motility involve intracellular transport of key molecules important for migration. Interestingly, a few studies indicate that Rabs can modulate the activity of Rho GTPases, important regulators for the cytoskeleton rearrangements, but the mechanisms behind this crosstalk are still poorly understood. In this work, we identify Rab6 as a negative regulator of cell migration in vitro and in vivo. We show that the loss of Rab6 promotes formation of actin protrusions and influences actomyosin dynamics by upregulating Cdc42 activity and downregulating myosin II phosphorylation. We further provide the molecular mechanism behind this regulation demonstrating that Rab6 interacts with both Cdc42 and Trio, a GEF for Cdc42. In sum, our results uncover a mechanism used by Rab proteins to ensure spatial regulation of Rho GTPase activity for coordination of cytoskeleton rearrangements required in migrating cells.
PMID: 30830239 [PubMed - as supplied by publisher]

Source: Cellular and Molecular Life Sciences : CMLS - March 3, 2019 Category: Cytology Authors: Vestre K, Kjos I, Guadagno NA, Borg Distefano M, Kohler F, Fenaroli F, Bakke O, Progida C Tags: Cell Mol Life Sci Source Type: research