- Tonucci FM, Hidalgo F, Ferretti A, Almada E, Favre C, Goldenring JR, Kaverina I, Kierbel A, Larocca MC. Centrosomal AKAP350 and CIP4 act in concert to define centrosome/Golgi polarity in migratory cells. Journal of Cell Science. 2015 Jul 24. PMID: 26208639 [PubMed].
The acquisition of a migratory phenotype is central in processes as diverse as embryo differentiation and tumor metastasis. An early event in this phenomenon is the generation of a nucleus-centrosome-Golgi back to front axis. AKAP350 is a Golgi/centrosome scaffold protein involved in microtubule nucleation. AKAP350 interacts with CIP4, a cdc42 effector that regulates actin dynamics. The present study aimed to characterize the participation of centrosomal AKAP350 in the acquisition of migratory polarity, and the involvement of CIP4 in the pathway. The decrease in total or in centrosomal AKAP350 led to decreased formation of the nucleus-centrosome-Golgi axis and defective cell migration. CIP4 localized at the centrosome. That was enhanced in migratory cells, but inhibited in cells with decreased centrosomal AKAP350. The interference with CIP4 expression or with CIP4/AKAP350 interaction also led to defective cell polarization. Centrosome positioning, but not nuclear movement was affected by loss of CIP4 or AKAP350 function. Our results support a model where AKAP350 recruits CIP4 to the centrosome, providing a centrosomal scaffold to integrate microtubule and actin dynamics, thus enabling centrosome polarization, and ensuring cell migration directionality.