Genetic suppressors of mrp-5 lethality in C. elegan | Posted on:2017-11-27 | Degree:M.S | Type:Thesis | University:University of Maryland, College Park | Candidate:Beardsley, Simon | Full Text:PDF | GTID:2463390011989960 | Subject:Genetics | Abstract/Summary: | | Heme is an essential cofactor in numerous proteins, but is also cytotoxic. Thus, directed pathways must exist for regulating heme homeostasis. C. elegans is a powerful genetic animal model for elucidating these pathways because it is a heme auxotroph. Worms acquire dietary heme though HRG-1-related importers, and intestinal export was demonstrated to be mediated by the ABC transporter MRP-5. Loss of mrp-5 results in embryonic lethality. Although heme transporters have been identified, there are significant gaps in our understanding for the heme trafficking beyond HRG-1 and MRP-5. To identify additional components, we conducted a forward genetic screen utilizing the null allele mrp-5(ok2067). Screening of 160,000 haploid genomes yielded thirty-two mrp-5(ok2067) suppressor mutants. Deep-sequencing variant analysis revealed three of the suppressors subunits of adapter protein complex 3 (AP-3). We now seek to identify mechanisms for how adaptor protein deficiencies bypass a defect in MRP-5-mediated heme export. | Keywords/Search Tags: | Mrp-5, Heme, Genetic | | Related items |
| |
|