title: Signaling Scaffold Protein IQGAP1 Interacts with Microtubule Plus-end Tracking Protein SKAP and Links Dynamic Microtubule Plus-end to Steer Cell Migration.
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.
authors.affiliation: 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.
authors.forename: Dan
authors.initials: D
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Zeqi
authors.initials: Z
authors.lastname: Su
authors.affiliation: 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.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Huihui
authors.initials: H
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027.
authors.forename: Saima
authors.initials: S
authors.lastname: Akram
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.affiliation: 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.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: 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.
authors.forename: Gregory
authors.initials: G
authors.lastname: Adams
authors.affiliation: From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: the Airforce General Hospital, Beijing, China 100036, and.
authors.forename: Lifang
authors.initials: L
authors.lastname: Liu
authors.affiliation: the Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Hill
authors.affiliation: From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027, wangdm@ustc.edu.cn.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.affiliation: From the BUCM-USTC Joint Program for Cellular Dynamics & Chemical Biology, University of Science & Technology of China, Hefei, China 230027.
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D020816:Amino Acid Motifs; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C101203:IQ motif containing GTPase activating protein 1; C555984:KNSTRN protein, human; D008869:Microtubule-Associated Proteins; D020703:ras GTPase-Activating Proteins; D004815:Epidermal Growth Factor
keywords: actin; cell migration; membrane; microtubule; microtubule dynamics; scaffold protein