Introduction The start point of cell generation occurs

Introduction

Prorenin receptor

The prorenin
receptor is a membrane-bound protein that is encoded by a gene found on the X
sex chromosome. The receptor protein is 350 amino acids long, made up of a large
extracellular domain with a weight of 28kDa and smaller transmembrane and cytoplasmic
domains, weight at 7kDA altogether. This receptor binds with high affinity to
both renin and its inactive precursor, prorenin, with their active sites
located on the extracellular domain. (biology of
the prorenin receptor).

 

A truncated
form of the prorenin receptor, consists of the transmembrane and cytoplasmic domains
and 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 muller
paper, 2010).  V-ATPase is found
in subcellular compartments such as the trans-Golgi network and vesicles. It
plays an important role in pH homeostasis to facilitate vital cellular
processes such as protein folding and membrane trafficking. As M8.9 and
V-ATPase are functionally linked, a mutation or deletion in the prorenin
receptor gene or protein itself, would affect these basic cellular processes (advani et al), causing cell
death.

 

The prorenin
receptor is highly conserved among species, with a 95% and 80% homology at the
nucleotide sequence and amino acid level respectively (biology of the prorenin receptor). The transmembrane and cytoplasmic
domains were found to be the most homologous part of the protein, indicating
that the cellular function these domains are involved in is vital to the
survival of the cell.

 

 

Link
between prorenin receptor and drosophila testes here

 

Drosophila testes and life cycle

     

Figure 1: Spermatogenesis in the Drosophila
Melanogaster testis — http://drosophila-images.org/2017

Figure 2: The drosophila stem cell niche — http://dev.biologists.org/content/138/14/2861.long#ref-29

 

The
Drosophila 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 the
tube (figure 2). Here, the hub cells are closely packed in a cluster consisting
of 10-15 cells. They are arranged in a dome shaped structure that protrudes
into the testis (http://dev.biologists.org/content/138/14/2861.long).
These hub cells provide a specialized niche environment via secreting molecules
to maintain the stem cell phenotype of germline stem cells (GSCs) and cyst stem
cells (cySCs) in the region (de Cuevas & Matunis, 2011 à honours paper).

 

The GSCs
are arranged around the hub cells, in a group of 10-12 cells (gary’s methods
paper). To exclude the stem cell phenotype maintenance factors secreted by the
hub cells, each GSC is enclosed and isolated by 2 cySCs (http://dx.doi.org/10.1016/j.cub.2016.07.012).
The cySCs communicate with the hub via cytoplasmic extensions, supporting the
homeostasis 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 form
spermatocytes, as part of spermatogenesis.

 

Drosophila as a model

Drosophila Melanogaster was the very first complex organism
to have its genome sequenced entirely. Upon completion of the sequencing of the
human genome, it was found that the two genomes were significantly homologous,
supporting the theory that the drosophila genome would serve as a good model to
understand human disease and biology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082451/

 

Good model
to 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.ncbi.nlm.nih.gov/pmc/articles/PMC3082451/

https://www.sciencedirect.com/science/article/pii/S1369702111701134

 

 

how the prorenin receptor relates to
infertility

–      
Is
it 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

–      
Quote
the podocyte and myocyte survival and suggest that it has strong evidence of
prr 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 UAS

Plan of
these project is to delete the prorenin receptor in cells at different cell
stages of spermatogenesis in the testis, and see how it affects the germ cell
count. Drivers used to target prorenin receptor in different cells.

–       obtain
driver information from trish

 

 

 

don’t do biblio till essay is finalized.