IntroductionProrenin receptorThe proreninreceptor is a membrane-bound protein that is encoded by a gene found on the Xsex chromosome.
The receptor protein is 350 amino acids long, made up of a largeextracellular domain with a weight of 28kDa and smaller transmembrane and cytoplasmicdomains, weight at 7kDA altogether. This receptor binds with high affinity toboth renin and its inactive precursor, prorenin, with their active siteslocated on the extracellular domain. (biology ofthe prorenin receptor).
A truncatedform of the prorenin receptor, consists of the transmembrane and cytoplasmic domainsand is named M8.9. https://www.ncbi.nlm.
nih.gov/pubmed/?term=The+(Pro)renin+Receptor%2FATP6AP2+is+Essential+for+Vacuolar+H%2B-ATPase+Assembly+in+Murine+Cardiomyocytes)It is coded by the ATP6ap2 gene and forms a complex with vacuolar H+-ATPase/V-ATPase (Genevieve nguyen + Dominik mullerpaper, 2010). V-ATPase is foundin subcellular compartments such as the trans-Golgi network and vesicles. Itplays an important role in pH homeostasis to facilitate vital cellularprocesses such as protein folding and membrane trafficking. As M8.9 andV-ATPase are functionally linked, a mutation or deletion in the proreninreceptor gene or protein itself, would affect these basic cellular processes (advani et al), causing celldeath.
The proreninreceptor is highly conserved among species, with a 95% and 80% homology at thenucleotide sequence and amino acid level respectively (biology of the prorenin receptor). The transmembrane and cytoplasmicdomains were found to be the most homologous part of the protein, indicatingthat the cellular function these domains are involved in is vital to thesurvival of the cell. Linkbetween prorenin receptor and drosophila testes here Drosophila testes and life cycle Figure 1: Spermatogenesis in the DrosophilaMelanogaster testis — http://drosophila-images.org/2017Figure 2: The drosophila stem cell niche — http://dev.biologists.
org/content/138/14/2861.long#ref-29 TheDrosophila testis is a blind-ended tube that each coil around a seminal vesicle(figure 1). The start point of cell generation occurs at the apical end of thetube (figure 2). Here, the hub cells are closely packed in a cluster consistingof 10-15 cells.
They are arranged in a dome shaped structure that protrudesinto the testis (http://dev.biologists.org/content/138/14/2861.long).These hub cells provide a specialized niche environment via secreting moleculesto maintain the stem cell phenotype of germline stem cells (GSCs) and cyst stemcells (cySCs) in the region (de Cuevas & Matunis, 2011 à honours paper). The GSCsare arranged around the hub cells, in a group of 10-12 cells (gary’s methodspaper). To exclude the stem cell phenotype maintenance factors secreted by thehub cells, each GSC is enclosed and isolated by 2 cySCs (http://dx.
012).The cySCs communicate with the hub via cytoplasmic extensions, supporting thehomeostasis of the stem cells and their derived cells lines (http://dev.biologists.org/content/138/14/2861.long#ref-29).
This allows the GSCs to undergo asymmetric division and differentiation to formspermatocytes, as part of spermatogenesis. Drosophila as a modelDrosophila Melanogaster was the very first complex organismto have its genome sequenced entirely. Upon completion of the sequencing of thehuman genome, it was found that the two genomes were significantly homologous,supporting the theory that the drosophila genome would serve as a good model tounderstand human disease and biology. https://www.ncbi.
nlm.nih.gov/pmc/articles/PMC3082451/ Good modelto study spermatogenesis as its life cycle is short, length of 9 days. Have Do research à how does studying drosophila,impact human medicine.https://www.
gov/pmc/articles/PMC3082451/https://www.sciencedirect.com/science/article/pii/S1369702111701134 how the prorenin receptor relates toinfertility- Isit only because of the vesicle trafficking and packaging à cellular processes cannot occur à cells die à the stem cells in the testis die à lesser cell sperm count- Quotethe podocyte and myocyte survival and suggest that it has strong evidence ofprr ablation to lead to the cells in the testes dying.- http://circres.ahajournals.org/content/107/1/30.long- https://www.
ncbi.nlm.nih.gov/pubmed/22034640 Project Plan – drivers, touch on UASPlan ofthese project is to delete the prorenin receptor in cells at different cellstages of spermatogenesis in the testis, and see how it affects the germ cellcount.
Drivers used to target prorenin receptor in different cells.- obtaindriver information from trish don’t do biblio till essay is finalized.