PROM1 - prominin 1 | Elisa - Clia - Antibody - Protein

Background

Prominin-1 (PROM1), also known as CD133, is a transmembrane glycoprotein that plays a significant role in stem cell biology and cellular development. Widely recognized as a marker for stem and progenitor cells in various tissues, PROM1 is expressed on the apical surface of epithelial and hematopoietic stem cells. It participates in cellular differentiation and is crucial for maintaining the stem cell niche, with implications in tissue regeneration and repair.

PROM1 has become a focus of research due to its role in cell signaling and its involvement in numerous developmental pathways, including those of the nervous system, retina, and digestive tract. Additionally, aberrant PROM1 expression is associated with cancer, specifically in cancer stem cells, and its presence is often used as a marker to identify cells with tumorigenic potential. PROM1’s relevance to cellular organization and tissue homeostasis, along with its association with pathological conditions, makes it an important molecule in cell biology and oncology.

Protein Structure

PROM1 is a five-transmembrane domain protein with a molecular weight of approximately 120 kDa. Its structure is highly conserved across species, which underscores its critical biological functions. The structural organization of PROM1 comprises three distinct extracellular loops, five transmembrane segments, and two significant intracellular regions:

Extracellular Domains:

• PROM1 has three prominent extracellular loops, particularly loop 1 and loop 3, which are substantial and contain multiple N-glycosylation sites. These glycosylation sites contribute to PROM1’s structural stability, protection from proteolytic cleavage, and functionality on the cell surface. These loops are also responsible for PROM1’s interaction with the cellular membrane’s lipid components, particularly with cholesterol-rich lipid microdomains, where PROM1 localizes.
• The extracellular domains are critical for the protein's role as a receptor or co-receptor in cell signaling. Their ability to bind ligands or interact with other cell surface molecules facilitates PROM1's involvement in various signaling pathways that regulate cell differentiation, apoptosis, and proliferation.

Transmembrane Domains:

• PROM1’s five transmembrane segments span the lipid bilayer, anchoring it firmly to the membrane. This arrangement is characteristic of proteins involved in signal transduction across the cell membrane.
• The positioning of these transmembrane domains allows PROM1 to interact with membrane lipids, particularly in lipid raft microdomains. This specific localization enables PROM1 to act as a scaffold, recruiting and organizing signaling molecules at the cell membrane. Its role in lipid rafts also contributes to its stability and facilitates its function in cellular signaling processes.

Intracellular Domains:

• The intracellular N-terminal and C-terminal domains are relatively short but essential for signal transduction. They contain binding motifs for adaptor proteins and other signaling molecules, allowing PROM1 to initiate or modulate downstream signaling events.
• These domains play a role in endocytosis and intracellular trafficking, which are important for PROM1’s dynamic presence on the cell surface and in various cellular compartments. The intracellular regions are also crucial for interactions with cytoskeletal elements, which assist in maintaining cellular structure and polarity.

Classification and Subtypes

PROM1 is classified as a pentaspan transmembrane glycoprotein and belongs to the prominin family of proteins. In humans, PROM1 is encoded by the PROM1 gene, which has several alternatively spliced isoforms. These isoforms differ in their N-terminal and C-terminal regions, affecting PROM1’s localization and function. The alternative splicing of PROM1 enables it to adapt its role in different tissues and cellular contexts, particularly in stem cells and progenitor cells.

Function and Biological Significance

PROM1 is integral to various cellular functions due to its role as a structural and signaling molecule. Its functions are particularly prominent in stem cell maintenance, cell polarity, and membrane organization:

Stem Cell Marker and Maintenance:

• PROM1 is widely used as a marker for identifying stem and progenitor cells, particularly in hematopoietic, neural, and epithelial tissues. It is associated with stem cell pluripotency and self-renewal. PROM1’s expression on the cell surface allows for the isolation and study of stem cell populations and their properties.
• Beyond merely being a marker, PROM1 also contributes to maintaining stem cell identity and regulating cellular differentiation. This function is critical in tissue development, regeneration, and repair processes, where PROM1-positive cells have the potential to replenish various tissue types.

Role in Cell Polarity and Membrane Organization:

• PROM1 is crucial in establishing and maintaining cellular polarity, particularly in epithelial cells, where it localizes to the apical membrane. This apical localization is essential for the formation and function of specialized structures, such as microvilli in the intestines and photoreceptor cells in the retina.
• By associating with cholesterol-rich lipid rafts, PROM1 organizes signaling molecules within these domains, supporting the precise orientation and function of cell surface receptors. This organization is necessary for cells that require a defined polarity for their functions, such as sensory cells and cells involved in nutrient absorption.

Role in Signal Transduction:

• PROM1 participates in various signaling pathways, such as the Wnt and Notch pathways, which are vital in cellular differentiation and development. Through these pathways, PROM1 influences cellular proliferation, migration, and survival, particularly in stem and progenitor cells.
• In the immune system, PROM1’s expression on hematopoietic stem cells plays a role in lymphoid and myeloid differentiation, impacting immune responses and hematopoiesis.

Clinical Issues

PROM1’s role in cell proliferation, differentiation, and its association with stem cells and cancer cells make it relevant in clinical settings:

Cancer:

• PROM1 is often overexpressed in cancer stem cells (CSCs) in tumors such as glioblastoma, colorectal cancer, hepatocellular carcinoma, and breast cancer. CSCs are thought to contribute to tumor initiation, metastasis, and resistance to therapy, and PROM1’s presence on these cells is associated with increased tumorigenic potential.
• Therapeutic strategies targeting PROM1-expressing CSCs are under investigation, aiming to improve treatment outcomes by addressing drug resistance and reducing the likelihood of relapse. Antibodies targeting PROM1 and PROM1-directed drug delivery systems are some of the approaches being explored.

Retinal Degeneration:

• Mutations in PROM1 are associated with degenerative retinal diseases such as retinitis pigmentosa and Stargardt-like macular dystrophy. PROM1 mutations impair photoreceptor structure and function, leading to progressive vision loss.
• Gene therapy aimed at correcting or compensating for defective PROM1 function is an area of ongoing research. The success of such therapies could offer treatment options for patients with PROM1-associated retinal disorders.

Neurological Disorders:

• PROM1 expression is also observed in the central nervous system, particularly in neural progenitor cells. Dysregulation of PROM1 expression or function may contribute to neurological diseases, especially those involving defective neurogenesis or neural degeneration.
• Research is ongoing to understand PROM1’s role in neurogenesis and neural repair, with potential implications for regenerative medicine targeting brain injuries and neurodegenerative diseases.

Hematopoietic Disorders:

• Since PROM1 is a marker for hematopoietic stem cells, aberrant PROM1 expression or mutations in its signaling pathway components could contribute to hematopoietic disorders. Its expression may serve as a prognostic marker or therapeutic target in certain blood cancers and immune disorders.

Summary

PROM1, also known as CD133, is a five-transmembrane glycoprotein essential for cellular polarity, stem cell maintenance, and organization within lipid raft microdomains. Structurally, it features three extracellular loops, five transmembrane domains, and intracellular regions that facilitate signaling, membrane organization, and intracellular trafficking. Classified within the prominin protein family, PROM1 is crucial in various tissues for regulating cell polarity and serving as a stem cell marker, particularly in epithelial and hematopoietic cells.

Clinically, PROM1 is relevant due to its association with cancer, retinal degeneration, and neurological and hematopoietic disorders. Its expression on cancer stem cells, in particular, has made it a target of therapeutic research, as these cells contribute to cancer progression and therapeutic resistance. In retinal degenerative diseases, PROM1 mutations result in vision loss, highlighting its importance in cellular development and structure. As a whole, PROM1 remains a focal point in stem cell biology, cancer research, and regenerative medicine, offering insights into cellular organization, differentiation, and potential therapeutic applications for various human diseases.