R-spondin-1 is a secreted protein that in humans is encoded by the ''Rspo1'' gene, found on chromosome 1. In humans, it interacts with WNT4 in the process of female sex development. Loss of function can cause female to male sex reversal. Furthermore, it promotes canonical WNT/β catenin signaling.
Structure
The protein has two
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, sometime ...
RSPO1 is required for the early development of gonads, regardless of sex. It has been found in mice only eleven days after fertilization. To induce cell proliferation, it acts synergistically with WNT4. They help stabilize β-catenin, which activates downstream targets. If both are deficient in XY mice, there is less expression of '' SRY'' and a reduction in the amount of
SOX9
Transcription factor SOX-9 is a protein that in humans is encoded by the ''SOX9'' gene.
Function
SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It is expressed by proliferating but no ...
. Moreover, defects in vascularization are found. These occurrences result in testicular
hypoplasia
Hypoplasia (from Ancient Greek ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.Leydig cells remain normal. They are maintained by steroidogenic cells, now unrepressed.
Ovaries
RSPO1 is necessary in female sex development. It augments the WNT/β catenin pathway to oppose male sex development. In critical gonadal stages, between six and nine weeks after fertilization, the ovaries upregulate it while the testes downregulate it.
Oral mucosa has been identified as a target tissue for RSPO1. When administered to normal mice, it causes nuclear translocation of β-catenin to this region. Modulation of the WNT/β catenin pathway occurs through the relief of Dkk1 inhibition. This occurrence results in increased basal cellularity, thickened mucosa, and elevated epithelial cell proliferation in the tongue. RSPO1 can therefore potentially aid in the treatment of mucositis, which is characterized by inflammation of the oral cavity. This unfortunate condition often accompanies chemotherapy and
radiation
In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes:
* ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...
in cancer patients with head and neck tumors. RSPO1 has also been shown to promote gastrointestinal epithelial cell proliferation in mice.