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Title | The mitotic role of adenomatous polyposis coli requires its bilateral interaction with tubulin and microtubules. |
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Journal, issue, pages | J Cell Sci, Vol. 136, Issue 2, Year 2023 |
Publish date | Jan 15, 2023 |
Authors | Laurence Serre / Julie Delaroche / Angélique Vinit / Guy Schoehn / Eric Denarier / Anne Fourest-Lieuvin / Isabelle Arnal / |
PubMed Abstract | Adenomatous polyposis coli (APC) is a scaffold protein with tumour suppressor properties. Mutations causing the loss of its C-terminal domain (APC-C), which bears cytoskeleton-regulating sequences, ...Adenomatous polyposis coli (APC) is a scaffold protein with tumour suppressor properties. Mutations causing the loss of its C-terminal domain (APC-C), which bears cytoskeleton-regulating sequences, correlate with colorectal cancer. The cellular roles of APC in mitosis are widely studied, but the molecular mechanisms of its interaction with the cytoskeleton are poorly understood. Here, we investigated how APC-C regulates microtubule properties, and found that it promotes both microtubule growth and shrinkage. Strikingly, APC-C accumulates at shrinking microtubule extremities, a common characteristic of depolymerases. Cryo-electron microscopy revealed that APC-C adopts an extended conformation along the protofilament crest and showed the presence of ring-like tubulin oligomers around the microtubule wall, which required the presence of two APC-C sub-domains. A mutant of APC-C that was incapable of decorating microtubules with ring-like tubulin oligomers exhibited a reduced effect on microtubule dynamics. Finally, whereas native APC-C rescued defective chromosome alignment in metaphase cells silenced for APC, the ring-incompetent mutant failed to correct mitotic defects. Thus, the bilateral interaction of APC-C with tubulin and microtubules likely contributes to its mitotic functions. |
External links | J Cell Sci / PubMed:36541084 |
Methods | EM (helical sym.) |
Resolution | 5.3 Å |
Structure data | EMDB-16435: microtubule decorated with tubulin oligomers in presence of APC C-terminal domain. (here only the microtubule map section is represented) |
Chemicals | ChemComp-TA1: ChemComp-GDP: ChemComp-MG: ChemComp-GTP: |
Source |
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Keywords | CELL CYCLE / cytoskeleton / microtubule |