PTGFRN - prostaglandin F2 receptor inhibitor|Elisa - Clia - Antibody - Protein

Background

Prostaglandin F2 receptor inhibitor (PTGFRN), also known as CD315 or FPRP (Fas-associated protein response-related protein), is a transmembrane protein associated with prostaglandin receptor signaling. PTGFRN is known primarily for its ability to modulate prostaglandin F2 alpha (PGF2α) receptor function, thereby impacting prostaglandin signaling pathways involved in inflammatory responses, immune modulation, and reproductive processes. PTGFRN doesn’t directly bind prostaglandins but instead influences PGF2α receptor function indirectly, regulating cellular responses to prostaglandins by modifying receptor sensitivity and availability on the cell surface.

PTGFRN has a wide tissue distribution and is expressed in cells of the immune system, cardiovascular tissues, reproductive organs, and certain epithelial tissues. Its role extends beyond prostaglandin modulation, as it’s also involved in various cellular processes including cell adhesion, migration, and interactions with other membrane proteins, such as tetraspanins. PTGFRN is therefore relevant in inflammatory diseases, reproductive health, cardiovascular function, and potentially in cancer.

Protein Structure

PTGFRN is a glycoprotein composed of several distinct structural features essential for its function and interactions with other proteins:

Extracellular Domain:

• PTGFRN has a large extracellular domain enriched with multiple N-glycosylation sites. Glycosylation is crucial for its proper folding, stability, and interactions with other cell surface proteins.
• This extracellular region is primarily responsible for interactions with tetraspanin proteins, such as CD9 and CD81, which are part of the tetraspanin-enriched microdomains (TEMs). These microdomains are specialized membrane regions that coordinate various signaling pathways by clustering receptors and other proteins.

Transmembrane Domain:

• PTGFRN has multiple transmembrane segments, suggesting it is embedded in the plasma membrane in a conformation that allows it to span the lipid bilayer multiple times. These transmembrane domains anchor PTGFRN to the cell membrane and are crucial for its stable expression and localization to TEMs.
• The transmembrane domains facilitate PTGFRN’s interactions with tetraspanins, which help regulate its spatial organization on the cell membrane and influence downstream signaling pathways.

Intracellular C-terminal Tail:

• PTGFRN contains a relatively short intracellular tail that lacks traditional signaling motifs found in many transmembrane receptors. However, it has several phosphorylation sites, which may modulate its interactions with other intracellular signaling molecules and adaptors.
• This domain’s modifications can affect PTGFRN’s ability to associate with intracellular scaffolding proteins, impacting its regulatory roles in cellular signaling pathways and receptor modulation.

Classification and Subtypes

PTGFRN is a member of the CD (cluster of differentiation) protein family and is also classified within the tetraspanin-associated proteins. While there are no known subtypes of PTGFRN, it is structurally and functionally similar to other cell surface receptors and tetraspanin-interacting proteins. PTGFRN does not directly function as a receptor or ligand; instead, it primarily serves as an accessory or regulatory protein. It is involved in forming molecular complexes with other surface proteins, contributing to the structure and function of tetraspanin-enriched microdomains.

Function and Biological Significance

PTGFRN’s biological functions are diverse, primarily due to its regulatory effects on prostaglandin signaling and interaction with membrane protein complexes:

Regulation of Prostaglandin F2α Signaling:

• PTGFRN modulates the function of the prostaglandin F2α receptor (FP receptor), impacting pathways involved in inflammation, smooth muscle contraction, and reproductive processes. By influencing receptor availability and function, PTGFRN indirectly controls PGF2α-mediated responses, which are essential in physiological processes such as uterine contraction, vascular tone, and inflammatory responses.

Association with Tetraspanins:

• PTGFRN interacts with tetraspanin proteins like CD9 and CD81, integrating into TEMs. These interactions are important for cellular adhesion, migration, and immune synapse formation. In TEMs, PTGFRN can help organize receptors and other proteins into functional clusters, facilitating effective signal transduction.
• This organization is particularly relevant in immune cells, where tetraspanin complexes help coordinate responses during immune surveillance, pathogen response, and intercellular communication.

Influence on Cell Adhesion and Migration:

• PTGFRN plays a role in cell adhesion and migration, particularly in the immune and vascular systems. Through its interaction with tetraspanins and other adhesion molecules, PTGFRN impacts the mobility and adhesion properties of cells, which are essential in immune cell trafficking and wound healing processes.

Role in Immune Function:

• PTGFRN expression in immune cells suggests a role in modulating immune responses. By forming complexes with receptors and tetraspanins, PTGFRN may influence processes like antigen presentation, cytokine production, and cell-to-cell communication, which are central to both innate and adaptive immune responses.

Potential Role in Reproductive Health:

• PTGFRN’s modulation of PGF2α signaling is particularly significant in reproductive tissues, where PGF2α plays a role in uterine contractions, parturition, and luteolysis. Dysregulation of PTGFRN expression or function in these tissues could potentially impact fertility and pregnancy outcomes.

Clinical Issues

PTGFRN is implicated in various clinical conditions due to its role in prostaglandin signaling and cellular adhesion:

Inflammatory Diseases:

• Given its role in modulating prostaglandin signaling, PTGFRN is associated with inflammatory responses. Alterations in PTGFRN expression can impact inflammation, which may contribute to conditions like arthritis, asthma, and chronic inflammatory diseases. Targeting PTGFRN interactions with the FP receptor could be a therapeutic strategy to regulate inflammation in these conditions.

Cancer:

• PTGFRN has been implicated in cancer due to its effects on cell adhesion, migration, and tetraspanin interactions. In tumors, PTGFRN may facilitate metastasis by enhancing cancer cell motility and adhesion, particularly in cancers like breast cancer and melanoma. Its association with tetraspanins may also influence tumor microenvironment interactions, which are critical in cancer progression.
• Overexpression of PTGFRN is observed in some tumor types, where it may contribute to tumor growth and metastasis. This makes PTGFRN a potential biomarker and therapeutic target in oncology.

Cardiovascular Disorders:

• PGF2α signaling is involved in vascular tone regulation, and PTGFRN modulation of this pathway may influence vascular function. Altered PTGFRN expression or function may contribute to cardiovascular diseases, including hypertension and atherosclerosis. Investigating PTGFRN’s role in vascular smooth muscle cells could help understand its impact on blood pressure regulation and arterial health.

Reproductive Disorders:

• Dysregulation of PTGFRN expression may impact PGF2α-mediated reproductive functions. Conditions such as dysmenorrhea (painful menstruation), preterm labor, and infertility could be linked to altered prostaglandin receptor modulation by PTGFRN. Targeting PTGFRN may offer therapeutic potential in managing prostaglandin-related reproductive disorders.

Autoimmune Diseases:

• PTGFRN’s role in immune cell interactions and prostaglandin signaling may influence autoimmune responses. Aberrant PTGFRN activity could contribute to autoimmune conditions like multiple sclerosis and rheumatoid arthritis by modulating immune cell adhesion, migration, and response to inflammation.

Summary

PTGFRN (CD315) is a multifunctional transmembrane protein involved in the modulation of prostaglandin F2α receptor activity and tetraspanin interactions. Its extracellular domain, with extensive glycosylation, supports binding with tetraspanins, positioning PTGFRN within TEMs that coordinate immune and inflammatory signaling. PTGFRN indirectly impacts prostaglandin signaling, immune responses, cell adhesion, and migration, making it relevant in inflammatory diseases, cancer, cardiovascular disorders, and reproductive health.

The clinical implications of PTGFRN span multiple fields, from oncology to immunology, due to its involvement in cell migration and immune modulation. Aberrant PTGFRN function or expression is linked to tumor metastasis, chronic inflammation, autoimmune diseases, and vascular conditions. This makes PTGFRN a potential target in therapeutic strategies aimed at modulating prostaglandin signaling, immune function, and cellular interactions, addressing a range of pathological conditions where these processes are dysregulated. Further research into PTGFRN could reveal new insights into its roles and therapeutic potential in various diseases.