Centrosomal AKAP350 and CIP4 act in concert to define centrosome/Golgi polarity in migratory cells

Abstract

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 nucleuscentrosome-Golgi back-to-front axis. AKAP350 (also known as AKAP9) is a Golgi and centrosome scaffold protein that is involved in microtubule nucleation. AKAP350 interacts with CIP4 (also known as TRIP10), 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-centrosomeGolgi axis and defective cell migration. CIP4 localized at the centrosome, which was enhanced in migratory cells, but inhibited in cells with decreased centrosomal AKAP350. A decrease in the CIP4 expression or inhibition of the 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 in which 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.

The Protein Encoded by the CCDC170 Breast Cancer Gene Functions to Organize the Golgi-Microtubule Network

“…PCM1). AKAP9 and MAP4 were of particular interest as AKAP9 was previously found to serve as a Golgi anchor ( Tonucci et al, 2015 , Sanders and Kaverina, 2015 ), in particular for CCDC165/MTCL1 ( Sato et al, 2014 ), while MAP4 functions to stabilize MTs ( Zahnleiter et al, 2015 , Andersen, 2000 ). As shown in Fig.…”

How alternative splicing affects membrane-trafficking dynamics

“…TRIP10 controls centrosome and Golgi polarization in migratory cells (Tonucci et al, 2015), E-cadherin trafficking during epithelial morphogenesis (Zobel et al, 2015), cell growth and invasion in cancer metastasis (Chander et al, 2012;Rolland et al, 2014;Truesdell et al, 2014), hypertrophy in neonatal cardiomyocytes (Rusconi et al, 2013), and GLUT4 trafficking in adipocytes (Chang et al, 2002). The N-terminus of TRIP10 contains the FCH domain and two coiled-coil domains, and mediates the interaction with AKAP350, tubulin and phospholipids.…”

Cdc42 and Cellular Polarity: Emerging Roles at the Golgi

“…This role of Cdc42 has been found to be dependent on microtubules, and also under the control of ARHGAP21, a protein that catalyzes the deactivation of Cdc42 [29]. More recently, AKAP350, a Golgi-localized protein involved in the nucleation of microtubules, has been found to interact with CIP4, which acts as an effector of Cdc42 in promoting the polarity of migrating cells [30]. …”