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
WNT4 is a secreted protein that, in humans, is encoded by the ''WNT4'' gene, found on chromosome 1. It promotes female sex development and represses male sex development. Loss of function may have consequences, such as female to male sex revers ...
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 chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
-rich,
furin-like domains and one
thrombospondin
Thrombospondins (TSPs) are a family of secreted glycoproteins with antiangiogenic functions. Due to their dynamic role within the extracellular matrix they are considered matricellular proteins. The first member of the family, thrombospondin 1 ...
type 1 domain.
Function
Sex development
Early gonads
RSPO1 is required for the early development of gonads, regardless of sex. It has been found in mice only eleven days after
fertilization
Fertilisation or fertilization (see American and British English spelling differences#-ise, -ize (-isation, -ization), spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give ...
.
To induce cell proliferation, it acts synergistically with
WNT4
WNT4 is a secreted protein that, in humans, is encoded by the ''WNT4'' gene, found on chromosome 1. It promotes female sex development and represses male sex development. Loss of function may have consequences, such as female to male sex revers ...
.
They help stabilize
β-catenin
Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcr ...
, which activates downstream targets. If both are deficient in XY mice, there is less expression of ''
SRY
Sex-determining region Y protein (SRY), or testis-determining factor (TDF), is a DNA-binding protein (also known as gene-regulatory protein/transcription factor) encoded by the ''SRY'' gene that is responsible for the initiation of male sex ...
'' 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 domain, DNA-binding proteins. It is expressed by ...
. Moreover, defects in vascularization are found. These occurrences result in testicular
hypoplasia
Hypoplasia (; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.Leydig cell
Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...
s 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
Fertilisation or fertilization (see American and British English spelling differences#-ise, -ize (-isation, -ization), spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give ...
, the ovaries upregulate it while the testes downregulate it.
Mucositis
Oral mucosa
The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed '' lamina propria''. The oral cavity has sometimes been des ...
has been identified as a target tissue for RSPO1. When administered to normal mice, it causes nuclear translocation of
β-catenin
Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcr ...
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
Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy and radiotherapy treatment for cancer. Mucositis can occur anywhere along the gastrointestinal (G ...
, which is characterized by inflammation of the oral cavity. This unfortunate condition often accompanies
chemotherapy
Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
and
radiation
In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or a material medium. This includes:
* ''electromagnetic radiation'' consisting of photons, such as radio waves, microwaves, infr ...
in cancer patients with head and neck tumors.
RSPO1 has also been shown to promote gastrointestinal epithelial cell proliferation in mice.
References
Further reading
*
*
*
*
*
*
*
*
*
*
External links
*
{{gene-1-stub
Glycoproteins
Extracellular matrix proteins