APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs
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...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Cell Insight |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772892724000658 |
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| author | Yong Wang Xinping Liu Zheng Liu Shasha Hua Kai Jiang |
| author_facet | Yong Wang Xinping Liu Zheng Liu Shasha Hua Kai Jiang |
| author_sort | Yong Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-32379c1f4bcc440bad3eee71ed0adac6 |
| institution | Kabale University |
| issn | 2772-8927 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Insight |
| spelling | doaj-art-32379c1f4bcc440bad3eee71ed0adac62025-01-30T05:15:17ZengElsevierCell Insight2772-89272025-02-0141100210APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPsYong Wang0Xinping Liu1Zheng Liu2Shasha Hua3Kai Jiang4State 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, ChinaThe 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, ChinaThe 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.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.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.http://www.sciencedirect.com/science/article/pii/S2772892724000658MicrotubuleAdenomatous polyposis coli proteinAPCCLASPsKIF2A |
| spellingShingle | Yong Wang Xinping Liu Zheng Liu Shasha Hua Kai Jiang APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs Cell Insight Microtubule Adenomatous polyposis coli protein APC CLASPs KIF2A |
| title | APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs |
| title_full | APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs |
| title_fullStr | APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs |
| title_full_unstemmed | APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs |
| title_short | APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs |
| title_sort | apc orchestrates microtubule dynamics by acting as a positive regulator of kif2a and a negative regulator of clasps |
| topic | Microtubule Adenomatous polyposis coli protein APC CLASPs KIF2A |
| url | http://www.sciencedirect.com/science/article/pii/S2772892724000658 |
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