CD164 - CD164 molecule | Elisa - Clia - Antibody - Protein

Background

CD164, also known as endolyn or sialomucin core protein 24 (MUC24), is a transmembrane protein involved in cell adhesion and cellular signaling. Expressed predominantly on the surface of hematopoietic progenitor cells and certain epithelial cells, CD164 plays a pivotal role in the regulation of cell migration, proliferation, and differentiation, especially within the hematopoietic system. Located on chromosome 6q21 in humans, the CD164 gene encodes a member of the sialomucin family, which is characterized by its extensive glycosylation and sialic acid residues. CD164 is a crucial molecule in hematopoiesis, as it contributes to the retention of hematopoietic stem cells (HSCs) in their niches and modulates the response of these cells to cytokines and growth factors.

Due to its significant roles in cell adhesion and migration, CD164 has been implicated in processes such as immune cell homing, tissue regeneration, and wound healing. Additionally, it plays a role in various diseases, including cancers, where it influences tumor cell migration and metastasis. CD164 is also a biomarker in specific cancer types and a regulator of cellular responses to inflammation.

Protein Structure

The CD164 protein has a complex structure that contributes to its roles in cell adhesion and migration. Key structural features of CD164 include:

Extracellular Domain:

• The extracellular domain of CD164 is heavily glycosylated and rich in sialic acid residues, which contribute to its role as a mucin-type protein. This domain contains serine and threonine-rich motifs that serve as glycosylation sites, enabling O-linked glycosylation. The sialic acid modifications confer a negative charge, which contributes to the adhesion properties of CD164 and its ability to interact with other cellular and extracellular components.
• The extracellular domain includes a cysteine-rich region with disulfide bonds, which stabilize the structure and enable interactions with extracellular matrix components and other cell surface molecules.

Transmembrane Domain:

• CD164 contains a single transmembrane helix that anchors it to the cell membrane. This domain is crucial for its role in signaling and mediating cell-cell interactions.
• The transmembrane region also facilitates the localization of CD164 within lipid rafts, specialized regions within the plasma membrane associated with signal transduction, which is important for modulating cellular responses to various stimuli.

Cytoplasmic Tail:

• The cytoplasmic region of CD164 contains specific amino acid motifs that interact with intracellular signaling molecules. Phosphorylation sites on this tail enable CD164 to participate in signaling pathways, allowing the receptor to influence cellular responses to external signals.
• This region also plays a role in the recruitment of adaptor proteins and signaling molecules, facilitating the activation of downstream pathways important for cell proliferation, migration, and differentiation.

Classification and Subtypes

CD164 belongs to the mucin family of cell adhesion molecules, specifically the sialomucin subfamily, characterized by extensive glycosylation and negatively charged sialic acid residues. Mucin proteins are often found on cell surfaces, where they mediate cell adhesion and modulate immune responses.

No distinct functional subtypes of CD164 have been characterized in humans, although alternative splicing events may result in minor variations. These isoforms may influence tissue-specific expression and subtle functional changes, although the overall function of CD164 is conserved across cell types where it is expressed.

Function and Biological Significance

CD164 is a multifunctional protein that participates in several biological processes:

Hematopoietic Stem Cell Regulation:

• One of CD164’s most critical functions is its role in hematopoietic stem cell (HSC) retention and migration within the bone marrow niche. It acts as a mediator between HSCs and the extracellular matrix, anchoring stem cells in their niches and preventing premature migration.
• CD164 modulates the interaction between HSCs and cytokines or growth factors, regulating stem cell activation, differentiation, and response to injury.

Cell Adhesion and Migration:

• Through its interactions with extracellular matrix components, CD164 plays a central role in cell adhesion and the migration of immune cells. It facilitates cellular movement, particularly in response to injury or inflammation, by mediating the interaction between cells and their microenvironments.
• In tissues, CD164 contributes to the migratory capacity of various cell types, including hematopoietic cells, mesenchymal stem cells, and epithelial cells, enabling efficient responses to regenerative and inflammatory signals.

Role in Immune Cell Homing and Activation:

• CD164 is involved in the homing and retention of immune cells in lymphoid organs and sites of inflammation. It mediates the adhesion and localization of immune cells, particularly T cells and monocytes, by interacting with other cell surface receptors and the extracellular matrix.
• By regulating the homing and retention of immune cells, CD164 helps modulate immune responses and inflammation, facilitating tissue repair and resolution of inflammation after injury or infection.

Tissue Regeneration and Wound Healing:

• CD164 contributes to tissue regeneration by modulating stem cell activity and migration in response to injury. Its interaction with cytokines and growth factors allows it to activate regenerative processes, supporting wound healing and tissue repair.

Clinical Issues

CD164 has been implicated in various diseases, particularly in cancer, where it influences tumor cell behavior, metastasis, and patient prognosis. Additionally, its involvement in immune cell function and inflammation makes CD164 relevant to autoimmune and inflammatory diseases.

Cancer:

• CD164 is overexpressed in several cancers, including prostate, breast, and colorectal cancers. Its role in cell adhesion and migration enhances tumor cell invasiveness and metastatic potential. Increased CD164 expression correlates with more aggressive cancer phenotypes and is often associated with poor prognosis.
• In cancers, CD164 promotes cancer cell interactions with the extracellular matrix and supports tumor growth by facilitating interactions with other growth factors and cytokines in the tumor microenvironment.

Autoimmune and Inflammatory Diseases:

• Given CD164’s role in immune cell homing and inflammation regulation, dysregulated CD164 expression may contribute to autoimmune diseases, where aberrant immune cell localization and activation are involved. Although direct associations are limited, CD164’s modulation of immune responses highlights its potential involvement in inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease.

Hematological Disorders:

• CD164’s function in HSC retention and migration suggests a potential role in hematological disorders. Altered expression or function of CD164 may disrupt hematopoiesis, contributing to diseases like leukemia or anemia by affecting stem cell behavior.

Biomarker Potential:

• Due to its overexpression in cancers and role in inflammation, CD164 serves as a potential biomarker for certain cancers and inflammatory conditions. Elevated levels of CD164 in tissue or blood samples can be indicative of disease progression, and it may aid in prognosis, particularly in cancers where high CD164 expression correlates with poor outcomes.

Summary

CD164 is a sialomucin family protein that mediates essential cellular functions, particularly in hematopoiesis, immune cell migration, and tissue repair. With a heavily glycosylated extracellular domain, a transmembrane region, and a signaling-competent cytoplasmic tail, CD164 anchors hematopoietic stem cells in their niches and regulates their response to cytokines. It also facilitates cell adhesion, migration, and immune cell localization, making it essential in tissue regeneration and immune regulation.

Clinically, CD164 is implicated in cancers, where it enhances tumor cell invasiveness and correlates with poorer prognosis. Its involvement in immune responses also makes it relevant to autoimmune and inflammatory diseases, while its function in HSC regulation highlights a potential role in hematological disorders. CD164’s biomarker potential in cancer and inflammation-associated diseases underscores its clinical significance, making it a target of interest for therapeutic intervention and disease monitoring.