Abstract
Rad21/Scc1 is a subunit of the cohesin complex implicated in gene regulation as well as sister chromatid cohesion. The level of Rad21/Scc1 must be controlled for proper mitosis and gene expression during development. Here, we identify the PP2A catalytic subunit encoded by microtubule star (mts) as a regulator of Drosophila Rad21/Verthandi (Vtd). Mutations in mts and vtd cause synergistic mitotic defects, including abnormal spindles and loss of nuclei during nuclear division in early embryo. Depletion of Mts and Vtd in developing wing synergistically reduces the Cut protein level, causing severe defects in wing growth. Mts and PP2A subunit Twins (Tws) interact with Vtd protein. Loss of Mts or Tws reduces Vtd protein level. Reduced proteasome function suppresses mitotic defects caused by mutations in mts and vtd. Taken together, this work provides evidence that PP2A is required for mitosis and wing growth by regulating the Vtd level through the proteasomal pathway.
Highlights
Phosphorylation is a key posttranslational mechanism for the regulation of cell signaling pathways
Dmt can restore mitotic defects of Sgo1-depleted human cells, indicating that Dmt has cohesin protection activity[34]. It is unknown whether Dmt and/or phosphatase 2A (PP2A) are required for the cohesin function in developing fly tissues and whether these proteins are involved in regulating the stability and the level of Cohesin complex proteins
To isolate protein partners that interact with Microtubule star (Mts), we screened a yeast two-hybrid library for Drosophila using a C-terminal Mts region that showed a low level of autoactivation
Summary
Phosphorylation is a key posttranslational mechanism for the regulation of cell signaling pathways. In Drosophila S2 cells, depletion of Vtd results in abnormal chromosome and spindle morphology with premature sister chromatid separation[10], consistent with the role of Rad21/Scc[1] for stabilizing the cohesin complex. Dmt can restore mitotic defects of Sgo1-depleted human cells, indicating that Dmt has cohesin protection activity[34] It is unknown whether Dmt and/or PP2A are required for the cohesin function in developing fly tissues and whether these proteins are involved in regulating the stability and the level of Cohesin complex proteins. It has been suggested that a major role of Mts in early Drosophila embryo is to link spindle microtubules to kinetochore since loss of Mts leads to spindle microtubules formed in random directions from centrosomes without association with chromosomes Another intriguing phenotype of mts loss-of-function mutations involves frequent loss of mitotic nuclei, resulting in free centrosomes separated from nuclei[8]. It is unknown whether cohesin subunit mutants show similar defects in Drosophila embryos
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
