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...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Cell Insight |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772892724000658 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 2772-8927 |