Date of Award

2023

Publication Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

Keywords

Anaphase promoting complex, APC/C coactivators, Drosophila, Meiosis, Cyclosome

Supervisor

A. Swan

Supervisor

J.Dason

Rights

info:eu-repo/semantics/openAccess

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

The E3 ubiquitin ligase, APC/C, is essential for the completion cell cycle; along with its co-activators it allows mitotic exit and maintenance of G1. APC/C marks various substrates with ubiquitin chains; marked substrates are subsequently destroyed via the 26S proteasome pathway. Cort is a Drosophila female meiosis specific activator of APC/C. Cort works within meiosis in conjunction with Fzy to mediate Securin and cyclin destruction. A C-terminal IR-tail motif and a N-terminal C-box support Cort-APC/C interaction, whereas short motifs like D-box and KEN-box on the target protein impart substrate recognition to Cort. Cort expression is tightly controlled in the female germline; and our lab found that misexpression of cort outside of this window results in a unique phenotype where females are transformed to male-like individuals. We provide evidence that this sex transformation is due to the actions of APC/CCort on the sex determination factor, Transformer (Tra). Genetic epistasis analysis showed that cort is partially epistatic to tra. Western blot analysis shows that in the presence of Cort, Traf (female isoform of Tra protein) levels go down significantly. This reduction of Traf levels is likely through APC/CCort mediated activity, as rendering APC/C ineffective via RNAi results in loss of sex transformation in Cort misexpressing individuals. Loss of maternal cort leads to reduced male viability and produce males with abnormal or missing genitalia and analia. This phenotype could potentially be a consequence of Traf weakly initiating the Sxl positive feedback loop in males. We hypothesize that maternal Cort mediated Traf destruction functions to safeguard the sexual morphology and viability of male progeny. We theorize that maternally deposited Cort is tasked with preventing untimely Sxl activation to ensure proper male development. This property of Tra could potentially have evolutionary implications for other Diptera species, where maternal Cort could target maternal Tra to stop male progeny from transforming into females.

Download

Share

COinS