RT Journal Article SR Electronic T1 Centrosome guides spatial activation of Rac to control cell polarization and directed cell migration JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800135 DO 10.26508/lsa.201800135 VO 2 IS 1 A1 Hung-Wei Cheng A1 Cheng-Te Hsiao A1 Yin-Quan Chen A1 Chi-Ming Huang A1 Seng-I Chan A1 Arthur Chiou A1 Jean-Cheng Kuo YR 2019 UL https://www.life-science-alliance.org/content/2/1/e201800135.abstract 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.