The Rac activator Tiam1 is required for polarized protrusional outgrowth of primary astrocytes by affecting the organization of the microtubule network.
Polarized cell migration is a crucial process in the development and repair of tissues, as well as in pathological conditions, including cancer. Recent studies have elucidated important roles for Rho GTPases in the establishment and maintenance of polarity prior to and during cell migration. Here, we show that Tiam1, a specific activator of the small GTPase Rac, is required for the polarized outgrowth of protrusions in primary astrocytes during the initial phase of cell polarization after scratch-wounding monolayers of cells. Tiam1 deficiency delays closure of wounds in confluent monolayers. Lack of Tiam1 impairs adoption of an asymmetrical cell shape as well as microtubule organization within protrusions. Positioning of the centrosome and Golgi apparatus, however, are independent of Tiam1-Rac signaling. We speculate that the function of Tiam1 in polarized outgrowth of astrocyte protrusions involves regulation of microtubule organization, possibly by stabilizing the microtubule cytoskeleton. Our results add Tiam1 as a player to the growing list of proteins involved in polarized outgrowth of protrusions and further elucidate the signaling pathways leading to cell polarization.
Division of Cell Biology I, The Netherlands Cancer Institute, Amsterdam, The Netherlands. s.ellenbroek@nki.nl and j.collard@nki.nl
Saskia I J
SI
Ellenbroek
Sandra
S
Iden
John G
JG
Collard
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D016764:Cell Polarity; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D055786:Gene Knockout Techniques; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1
D020662:Guanine Nucleotide Exchange Factors; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C513260:Tiam1 protein, mouse