PT - JOURNAL ARTICLE AU - Hung-Wei Cheng AU - Cheng-Te Hsiao AU - Yin-Quan Chen AU - Chi-Ming Huang AU - Seng-I Chan AU - Arthur Chiou AU - Jean-Cheng Kuo TI - Centrosome guides spatial activation of Rac to control cell polarization and directed cell migration AID - 10.26508/lsa.201800135 DP - 2019 Feb 01 TA - Life Science Alliance PG - e201800135 VI - 2 IP - 1 4099 - https://www.life-science-alliance.org/content/2/1/e201800135.short 4100 - https://www.life-science-alliance.org/content/2/1/e201800135.full SO - Life Sci. Alliance2019 Feb 01; 2 AB - Directed cell migration requires centrosome-mediated cell polarization and dynamical control of focal adhesions (FAs). To examine how FAs cooperate with centrosomes for directed cell migration, we used centrosome-deficient cells and found that loss of centrosomes enhanced the formation of acentrosomal microtubules, which failed to form polarized structures in wound-edge cells. In acentrosomal cells, we detected higher levels of Rac1-guanine nucleotide exchange factor TRIO (Triple Functional Domain Protein) on microtubules and FAs. Acentrosomal microtubules deliver TRIO to FAs for Rac1 regulation. Indeed, centrosome disruption induced excessive Rac1 activation around the cell periphery via TRIO, causing rapid FA turnover, a disorganized actin meshwork, randomly protruding lamellipodia, and loss of cell polarity. This study reveals the importance of centrosomes to balance the assembly of centrosomal and acentrosomal microtubules and to deliver microtubule-associated TRIO proteins to FAs at the cell front for proper spatial activation of Rac1, FA turnover, lamillipodial protrusion, and cell polarization, thereby allowing directed cell migration.