The CAMSAP3-ACF7 Complex Couples Noncentrosomal Microtubules with Actin Filaments to Coordinate Their Dynamics.
For adaptation to complex cellular functions, dynamic cytoskeletal networks are required. There are two major components of the cytoskeleton, microtubules and actin filaments, which form an intricate network maintaining an exquisite cooperation to build the physical basis for their cellular function. However, little is known about the molecular mechanism underlying their synergism. Here, we show that in Caco2 epithelial cells, noncentrosomal microtubules crosstalk with F-actin through their minus ends and contribute to the regulation of focal adhesion size and cell migration. We demonstrate that ACF7, a member of the spectraplakin family of cytoskeletal crosslinking proteins, interacts with Nezha (also called CAMSAP3) at the minus ends of noncentrosomal microtubules and anchors them to actin filaments. Those noncentrosomal microtubules cooperate with actin filaments through retrograde flow to keep their length and orientation perpendicular to the cell edge as well as regulate focal adhesion size and cell migration.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Zhongguancun South Road, Haidian District, Beijing 100190, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Wenxiu
W
Ning
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Zhongguancun South Road, Haidian District, Beijing 100190, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Yanan
Y
Yu
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Zhongguancun South Road, Haidian District, Beijing 100190, China.
Honglin
H
Xu
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Zhongguancun South Road, Haidian District, Beijing 100190, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Xiaofei
X
Liu
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Zhongguancun South Road, Haidian District, Beijing 100190, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Daiwei
D
Wang
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Zhongguancun South Road, Haidian District, Beijing 100190, China.
Jing
J
Wang
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Zhongguancun South Road, Haidian District, Beijing 100190, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Yingchun
Y
Wang
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Zhongguancun South Road, Haidian District, Beijing 100190, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: wxmeng@genetics.ac.cn.
Wenxiang
W
Meng
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D018938:Caco-2 Cells; D002465:Cell Movement; D018385:Centrosome / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C000608274:Camsap3 protein, human; C095003:MACF1 protein, human; C588005:MAPRE2 protein, human
ACF7; Nezha/CAMSAP3; actin; cell migration; noncentrosomal microtubules; retrograde flow