Tumor suppressor APC is an attenuator of spindle-pulling forces during asymmetric cell division
| Autor: | Sugioka, Kenji, Fielmich, Lars-Eric, Mizumoto, Kota, Bowerman, Bruce, van den Heuvel, Sander, Kimura, Akatsuki, Sawa, Hitoshi |
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| Přispěvatelé: | Sub Developmental Biology, Developmental Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Caenorhabditis elegans/cytology
Cell Cycle Proteins/metabolism Zygote Adenomatous Polyposis Coli Protein/metabolism Asymmetric Cell Division Cell Polarity Spindle Apparatus Tubulin/metabolism Models Theoretical Cytoplasm/metabolism Centrosome/metabolism Microtubules/metabolism Mutation Animals Computer Simulation RNA Interference Caenorhabditis elegans Proteins/metabolism Stress Mechanical CRISPR-Cas Systems Green Fluorescent Proteins/metabolism |
| Popis: | The adenomatous polyposis coli (APC) tumor suppressor has dual functions in Wnt/β-catenin signaling and accurate chromosome segregation and is frequently mutated in colorectal cancers. Although APC contributes to proper cell division, the underlying mechanisms remain poorly understood. Here we show that Caenorhabditis elegans APR-1/APC is an attenuator of the pulling forces acting on the mitotic spindle. During asymmetric cell division of the C. elegans zygote, a LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate pulling forces on astral microtubules that position the mitotic spindle. We found that APR-1 localizes to the anterior cell cortex in a Par-aPKC polarity-dependent manner and suppresses anterior centrosome movements. Our combined cell biological and mathematical analyses support the conclusion that cortical APR-1 reduces force generation by stabilizing microtubule plus-ends at the cell cortex. Furthermore, APR-1 functions in coordination with LIN-5 phosphorylation to attenuate spindle-pulling forces. Our results document a physical basis for the attenuation of spindle-pulling force, which may be generally used in asymmetric cell division and, when disrupted, potentially contributes to division defects in cancer. |
| Databáze: | OpenAIRE |
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