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, Sub Developmental Biology, Developmental Biology |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell division Caenorhabditis elegans/cytology Adenomatous polyposis coli Zygote Spindle Apparatus Stress 03 medical and health sciences 0302 clinical medicine Theoretical Models Cell cortex Asymmetric cell division Animals Computer Simulation Green Fluorescent Proteins/metabolism Multidisciplinary biology Cell Cycle Proteins/metabolism Adenomatous Polyposis Coli Protein/metabolism Asymmetric Cell Division Cell Polarity Tubulin/metabolism Models Theoretical Mechanical Cell biology Spindle apparatus Cytoplasm/metabolism Centrosome/metabolism 030104 developmental biology Microtubules/metabolism Centrosome Mutation biology.protein RNA Interference Caenorhabditis elegans Proteins/metabolism Stress Mechanical CRISPR-Cas Systems Astral microtubules 030217 neurology & neurosurgery Anterior cell cortex |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 115(5), E954. National Academy of Sciences |
| ISSN: | 0027-8424 |
| 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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