Big roles for small GTPases in the control of directed cell movement

Charest, Pascale G.; Firtel, Richard A.

doi:10.1042/bj20061432

Cited by 179 publications

(157 citation statements)

References 213 publications

(295 reference statements)

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“…RasGRF2 promotes exchange activities on both Ras and Rac GTPases (34); activation of either pathway can have profound effects on actin remodeling and cancer cell migration (35). A recent study showed that RasGRF2 regulates cancer cell invasion through direct binding to Cdc42 thereby sequestering it from association with cognate GEFs, and knockdown of RasGRF2 increased rounded invasion of melanoma cells (36).…”

Section: Discussionmentioning

confidence: 99%

βArrestin1 Regulates the Guanine Nucleotide Exchange Factor RasGRF2 Expression and the Small GTPase Rac-mediated Formation of Membrane Protrusion and Cell Motility

España‐Serrano

Kim

et al. 2014

Journal of Biological Chemistry

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Background: G protein-coupled receptors (GPCRs) and ␤arrestins have been shown to regulate cell motility. Results: ␤Arrestin1 regulates cell migration through RasGRF2 (a dual guanine nucleotide exchange factor) gene expression and the small GTPase Rac activity. Conclusion: ␤Arrestin1 may regulate cellular functions at the gene expression level. Significance: ␤Arrestins may function at transcriptional and post-translational levels to regulate cell migration.

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Section: Discussionmentioning

confidence: 99%

βArrestin1 Regulates the Guanine Nucleotide Exchange Factor RasGRF2 Expression and the Small GTPase Rac-mediated Formation of Membrane Protrusion and Cell Motility

España‐Serrano

Kim

et al. 2014

Journal of Biological Chemistry

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“…Candidates for such regulatory roles include members of the Rho-GTPase family of molecules, such as Rho and Rac1, which translate external signals into alterations in cytoskeletal reorganization and hence have the ability to influence migration. A large body of literature has characterized the cellular mechanisms and signal transduction pathways of Rho, Rho-dependent kinase (ROCK) and related regulatory members, such as Rac and PI3K, on cellular motility and chemotaxis in various cell types [29][30][31][32][33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

et al. 2011

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Adult neural precursor cells (NPCs) in the subventricular zone (SVZ) normally migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB). Following neural injury, they also migrate to the site of damage. This study investigated the role of Rho-dependent kinase (ROCK) on the migration of NPCs in vitro and in vivo. In vitro, using neurospheres or SVZ explants, inhibition of ROCK using Y27632 promoted cell body elongation, process protrusion, and migration, while inhibiting NPC chain formation. It had no effect on proliferation, apoptosis, or differentiation. Both isoforms of ROCK were involved. Using siRNA, knockdown of both ROCK1 and ROCK2 was required to promote NPC migration and morphological changes; knockdown of ROCK2 alone was partially effective, with little/no effect of knockdown of ROCK1 alone. In vivo, infusion of Y27632 plus Bromodeoxyuridine (BrdU) into the lateral ventricle for 1 week reduced the number of BrdU-labeled NPCs in the OB compared with BrdU infusion alone. However, ROCK inhibition did not affect the tangential-to-radial switch of NPC migration, as labeled cells were present in all OB layers. The decrease in NPC number at the OB was not attributed to a decrease in NPCs at the SVZ. However, ROCK inhibition decreased the density of BrdU-labeled cells in the RMS and increased the distribution of these cells to ectopic brain regions, such as the accessory olfactory nucleus, where the majority differentiated into neurons. These findings suggest that ROCK signaling regulates NPC migration via regulation of cell-cell contact and chain migration.

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“…The small G-proteins, Cdc42, Rac and Rho, seem to be at the heart of the initial signals leading to the polarization of migrating cells (Charest and Firtel, 2007). They participate in cell migration by regulating cytoskeletal reorganization, a prerequisite for cell motility (Etienne-Manneville and Hall, 2002;Charest and Firtel, 2007).…”

Section: Cell Polarity Is Essential In Cell Migrationmentioning

confidence: 99%