NPP-21/TPR is required for developmental control of spindle checkpoint strength in C. elegans

NPP-21/TPR是秀丽隐杆线虫纺锤体检查点强度发育调控所必需的

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Abstract

The spindle checkpoint ensures accurate chromosome segregation by monitoring whether chromosomes, via kinetochores, are properly attached to the mitotic or meiotic spindle. If chromosomes are unattached, the checkpoint delays the cell cycle to facilitate error correction. In C. elegans early embryos, activation of the spindle checkpoint produces a longer mitotic delay in cells that will become germline tissue than in cells that will become somatic tissue, suggesting developmental regulation. We show that the conserved nucleoporin and spindle matrix component, NPP-21/TPR, is required for the stronger spindle checkpoint in germline cells. A strain expressing AID-3xFLAG-NPP-21 and the Arabidopsis TIR1 gene cannot support the stronger checkpoint in germline cells. When AID-3xFLAG-NPP-21 is acutely degraded, the checkpoint in germline cells is further compromised while somatic cells are unaffected. A checkpoint-proficient NPP-21-GFP transgene localizes to a spindle-like structure during mitosis and is enriched in germline cells, consistent with a cell-fate specific function for this protein. Finally, NPP-21 controls spindle checkpoint strength in germline cells by two, potentially linked, control points: concentrating PCH-2 around mitotic chromosomes and promoting the localization of the checkpoint effector, Mad2, to unattached kinetochores. These experiments demonstrate a developmental role for NPP-21, and the spindle matrix, in controlling spindle checkpoint strength in immortal germline cells in C. elegans .

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