Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Centrosome guides spatial activation of Rac to control cell polarization and directed cell migration (#634)

Hung-Wei Cheng 1 , Cheng-Te Hsiao 2 , Yin-Quan Chen 3 , Chi-Ming Huang 1 , Seng-I Chan 1 , Arthur Chiou 4 , Jean-Cheng Kuo 1 3
  1. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan
  2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
  3. Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan
  4. Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan

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-GEF TRIO 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 as well as 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 for directed cell migration.