APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs
Yong Wang,
Xinping Liu,
Zheng Liu,
Shasha Hua,
Kai Jiang
Affiliations
Yong Wang
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Medical Research Institute, Wuhan University, Wuhan, 430071, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430071, China
Xinping Liu
The Institute for Advanced Studies, TaiKang Center for Life and Medical Sciences, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China
Zheng Liu
The Institute for Advanced Studies, TaiKang Center for Life and Medical Sciences, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China; Corresponding author.
Shasha Hua
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Medical Research Institute, Wuhan University, Wuhan, 430071, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430071, China; Corresponding author. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Medical Research Institute, Wuhan University, Wuhan, 430071, China.
Kai Jiang
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Medical Research Institute, Wuhan University, Wuhan, 430071, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430071, China; Corresponding author. Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430071, China.
Tumor suppressor protein Adenomatous polyposis coli protein (APC) is an EB-binding and microtubule (MT) plus end-tracking protein; however, how exactly APC regulates MT dynamics remains elusive. Here, we show that in LLC-PK1 cells, APC and KIF2A, an MT depolymerase, form a complex clustering at the cell edge and destabilize MTs at the MT plus ends. Further biochemical characterization and mutational analysis reveal key residues for the APC-KIF2A interaction. In addition, APC counteracts the major MT-stabilizer CLASPs at MT plus ends and promotes directional cell migration via modulating cell adhesion force. Reconstitution experiments demonstrate that APC potentiates KIF2A-induced MT catastrophes and antagonizes the stabilizing effect of CLASP2 in vitro. In summary, APC functions as a positive regulator of MT-destabilizer and a negative regulator of MT-stabilizer to orchestrate MT dynamics.
