Signaling Scaffold Protein IQGAP1 Interacts with Microtubule Plus-end Tracking Protein SKAP and Links Dynamic Microtubule Plus-end to Steer Cell Migration

J Biol Chem. 2015 Sep 25;290(39):23766-80. doi: 10.1074/jbc.M115.673517.

Dan Cao ¹, Zeqi Su ², Wenwen Wang ¹, Huihui Wu ³, Xing Liu ⁴, Saima Akram ⁵, Bo Qin ³, Jiajia Zhou ⁶, Xiaoxuan Zhuang ⁵, Gregory Adams ⁷, Changjiang Jin ⁵, Xiwei Wang ⁷, Lifang Liu ⁸, Donald L Hill ⁹, Dongmei Wang ¹⁰, Xia Ding ¹¹, Xuebiao Yao ⁵

Affiliations

1 From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027, the Beijing University of Chinese Medicine, Beijing, China 100029, the Morehouse School of Medicine, Atlanta, Georgia 30310.
2 From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027, the Beijing University of Chinese Medicine, Beijing, China 100029.
3 From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027, the Morehouse School of Medicine, Atlanta, Georgia 30310, the Airforce General Hospital, Beijing, China 100036, and.
4 From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027, the Beijing University of Chinese Medicine, Beijing, China 100029, the Morehouse School of Medicine, Atlanta, Georgia 30310, xing1017@ustc.edu.cn.
5 From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027.
6 From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027, the Airforce General Hospital, Beijing, China 100036, and.
7 From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027, the Morehouse School of Medicine, Atlanta, Georgia 30310.
8 the Airforce General Hospital, Beijing, China 100036, and.
9 the Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294.
10 From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027, wangdm@ustc.edu.cn.
11 From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027, the Beijing University of Chinese Medicine, Beijing, China 100029, ding-bucm@hotmail.com ustclcd@ustc.edu.cn.

PMID: 26242911 DOI: 10.1074/jbc.M115.673517

Abstract

Cell migration is orchestrated by dynamic interaction of microtubules with the plasma membrane cortex. However, the regulatory mechanisms underlying the cortical actin Cytoskeleton and microtubule dynamics are less characterized. Our earlier study showed that small GTPase-activating proteins, IQGAPs, regulate polarized secretion in epithelial cells (1). Here, we show that IQGAP1 links dynamic microtubules to steer cell migration via interacting with the plus-end tracking protein, SKAP. Biochemical characterizations revealed that IQGAP1 and SKAP form a cognate complex and that their binding interfaces map to the WWIQ motif and the C-terminal of SKAP, respectively. The WWIQ peptide disrupts the biochemical interaction between IQGAP1 and SKAP in vitro, and perturbation of the IQGAP1-SKAP interaction in vivo using a membrane-permeable TAT-WWIQ peptide results in inhibition of directional cell migration elicited by EGF. Mechanistically, the N-terminal of SKAP binds to EB1, and its C terminus binds to IQGAP1 in migrating cells. Thus, we reason that a novel IQGAP1 complex orchestrates directional cell migration via coupling dynamic microtubule plus-ends to the cell cortex.

Keywords

actin; cell migration; membrane; microtubule; microtubule dynamics; scaffold protein.

Name
Email *

	Sorry, but the email address you supplied was invalid.