PT  - JOURNAL ARTICLE
AU  - Kenji Sugioka
AU  - Lars-Eric Fielmich
AU  - Kota Mizumoto
AU  - Bruce Bowerman
AU  - Sander van den Heuvel
AU  - Akatsuki Kimura
AU  - Hitoshi Sawa
TI  - The tumor suppressor APC is an attenuator of spindle-pulling forces during <em>C. elegans</em> asymmetric cell division
AID  - 10.1101/157404
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 157404
4099  - http://biorxiv.org/content/early/2017/06/30/157404.short
4100  - http://biorxiv.org/content/early/2017/06/30/157404.full
AB  - 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 C. 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 spindle-pulling force attenuation, which may be generally used in asymmetric cell division, and when disrupted potentially contributes to division defects in cancer.