Endocytic trafficking of Rac is required for the spatial restriction of signaling in cell migration
- PMID: 18614017
- DOI: 10.1016/j.cell.2008.05.034
Endocytic trafficking of Rac is required for the spatial restriction of signaling in cell migration
Abstract
The small GTPases, Rab5 and Rac, are essential for endocytosis and actin remodeling, respectively. Coordination of these processes is critical to achieve spatial restriction of intracellular signaling, which is essential for a variety of polarized functions. Here, we show that clathrin- and Rab5-mediated endocytosis are required for the activation of Rac induced by motogenic stimuli. Rac activation occurs on early endosomes, where the RacGEF Tiam1 is also recruited. Subsequent recycling of Rac to the plasma membrane ensures localized signaling, leading to the formation of actin-based migratory protrusions. Thus, membrane trafficking of Rac is required for the spatial resolution of Rac-dependent motogenic signals. We further demonstrate that a Rab5-to-Rac circuitry controls the morphology of motile mammalian tumor cells and primordial germinal cells during zebrafish development, suggesting that this circuitry is relevant for the regulation of migratory programs in various cells, in both in vitro settings and whole organisms.
Comment in
-
Rab5 and rac team up in cell motility.Cell. 2008 Jul 11;134(1):18-20. doi: 10.1016/j.cell.2008.06.039. Cell. 2008. PMID: 18614005
Similar articles
-
Probing E-cadherin endocytosis by morpholino-mediated Rab5 knockdown in zebrafish.Methods Mol Biol. 2008;440:371-87. doi: 10.1007/978-1-59745-178-9_27. Methods Mol Biol. 2008. PMID: 18369959
-
Interplay between Rab5 and PtdIns(4,5)P2 controls early endocytosis in the Drosophila germline.J Cell Sci. 2009 Jan 1;122(Pt 1):25-35. doi: 10.1242/jcs.033027. Epub 2008 Dec 2. J Cell Sci. 2009. PMID: 19050045
-
Role of Rab5 in insulin receptor-mediated endocytosis and signaling.Arch Biochem Biophys. 2006 May 15;449(1-2):130-42. doi: 10.1016/j.abb.2006.01.020. Epub 2006 Mar 3. Arch Biochem Biophys. 2006. PMID: 16554017
-
Vps9 domain-containing proteins: activators of Rab5 GTPases from yeast to neurons.Trends Cell Biol. 2006 Jan;16(1):27-35. doi: 10.1016/j.tcb.2005.11.001. Epub 2005 Dec 2. Trends Cell Biol. 2006. PMID: 16330212 Review.
-
Pathways linking endocytosis and actin cytoskeleton in mammalian cells.Exp Cell Res. 2001 Nov 15;271(1):45-56. doi: 10.1006/excr.2001.5369. Exp Cell Res. 2001. PMID: 11697881 Review. No abstract available.
Cited by
-
WAVE/SCAR promotes endocytosis and early endosome morphology in polarized C. elegans epithelia.Dev Biol. 2013 May 15;377(2):319-32. doi: 10.1016/j.ydbio.2013.03.012. Epub 2013 Mar 17. Dev Biol. 2013. PMID: 23510716 Free PMC article.
-
The functional interplay of Rab11, FIP3 and Rho proteins on the endosomal recycling pathway controls cell shape and symmetry.Small GTPases. 2018 Jul 4;9(4):310-315. doi: 10.1080/21541248.2016.1224288. Epub 2016 Sep 2. Small GTPases. 2018. PMID: 27533792 Free PMC article. Review.
-
MicroRNA-130a inhibits cell proliferation, invasion and migration in human breast cancer by targeting the RAB5A.Int J Clin Exp Pathol. 2015 Jan 1;8(1):384-93. eCollection 2015. Int J Clin Exp Pathol. 2015. PMID: 25755726 Free PMC article.
-
Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem cells/progenitors through endothelial AT₂R and cytoskeletal dysregulation.Nat Commun. 2015 Jan 9;6:5914. doi: 10.1038/ncomms6914. Nat Commun. 2015. PMID: 25574809 Free PMC article.
-
Rabenosyn-5 suppresses non-small cell lung cancer metastasis via inhibiting CDC42 activity.Cancer Gene Ther. 2024 Oct;31(10):1465-1476. doi: 10.1038/s41417-024-00813-4. Epub 2024 Jul 29. Cancer Gene Ther. 2024. PMID: 39075137 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous
