ITGA1 - integrin subunit alpha 1 |Elisa - Clia - Antibody - Protein

Background

Integrin subunit alpha 1 (ITGA1) is a member of the integrin family, a group of transmembrane receptors involved in cell-extracellular matrix (ECM) adhesion and cell-cell interactions. Integrins are heterodimeric molecules composed of an alpha and beta subunit that combine to form functional receptors. These receptors are critical for mediating cell adhesion, migration, proliferation, and signal transduction across the plasma membrane. ITGA1, specifically, pairs with integrin beta 1 (ITGB1) to form the α1β1 integrin, which primarily serves as a receptor for collagen and laminin in the extracellular matrix.

The ITGA1 gene, located on chromosome 5q11.2, encodes the alpha 1 subunit, which is involved in binding to collagen types I and IV. This binding plays a significant role in the regulation of cellular responses such as matrix remodeling, wound healing, inflammation, and cell differentiation. ITGA1 expression is found across various tissues, including the kidney, liver, smooth muscle cells, fibroblasts, and immune cells, reflecting its diverse physiological functions. Additionally, ITGA1 has emerged as an important player in tumor biology, where it can influence cancer cell adhesion, invasion, and metastasis.

Protein Structure

The integrin alpha 1 (ITGA1) protein is a transmembrane glycoprotein that is structurally and functionally designed to interact with the extracellular matrix and transmit signals intracellularly. It has the following distinct regions:

Extracellular Domain:

• ITGA1 has a large extracellular domain of approximately 1000 amino acids, which is responsible for ligand binding and ECM interactions. This domain contains seven repeats known as integrin epidermal growth factor-like (EGF-like) repeats and a vWFA (von Willebrand factor type A) domain, which is crucial for collagen binding.
• The vWFA domain, also known as the I-domain or inserted domain, mediates the interaction of ITGA1 with collagen types I and IV, playing a key role in cell adhesion. This binding is facilitated by the presence of divalent cations, such as Mg²⁺ or Mn²⁺, which regulate the ligand-binding affinity.
• The extracellular domain is heavily glycosylated, which stabilizes the protein structure and modulates its interactions with ligands.

Transmembrane Domain:

• ITGA1 has a single transmembrane helix, spanning approximately 20-25 amino acids, that anchors the protein within the plasma membrane. The transmembrane domain is essential for the physical connection between the extracellular matrix and the cytoplasmic signaling pathways.
• This region is also involved in heterodimer formation with the integrin beta 1 (ITGB1) subunit, ensuring proper receptor function.

Cytoplasmic Domain:

• The cytoplasmic tail of ITGA1 is relatively short, comprising about 20-50 amino acids, but plays a crucial role in intracellular signal transduction. It interacts with various cytoskeletal and signaling proteins, such as talin, kindlin, and paxillin, to mediate inside-out and outside-in signaling.
• Through these interactions, ITGA1 can regulate cellular processes such as cytoskeletal rearrangement, cell spreading, and migration. Additionally, phosphorylation of specific residues within the cytoplasmic domain can modulate integrin activity and its interaction with other intracellular proteins.

Heterodimerization:

• ITGA1 pairs with integrin beta 1 (ITGB1) to form the α1β1 integrin heterodimer. The heterodimerization is critical for the receptor's ability to bind to ECM components such as collagen and laminin. The dimerization occurs via non-covalent interactions between the extracellular and transmembrane regions of the alpha and beta subunits.
• This α1β1 integrin heterodimer has a specialized role in recognizing and binding collagen-rich matrices, such as those found in the basement membrane and other stromal tissues.

Classification and Subtypes

ITGA1 is a part of the larger integrin family, which consists of 24 heterodimers formed by the combination of 18 alpha and 8 beta subunits. These integrins are classified based on their ligand specificity and biological functions. The α1β1 integrin, formed by the ITGA1 and ITGB1 subunits, is classified primarily as a collagen receptor.

There are no well-established subtypes of ITGA1, but its functional diversity is largely determined by its heterodimeric partner (ITGB1) and the cellular context in which it is expressed.

Function and Biological Significance

ITGA1 plays several essential roles in regulating cellular responses to the extracellular environment. Its primary functions include:

Cell Adhesion and Migration:

• ITGA1 is critically involved in cell adhesion to the extracellular matrix, particularly to collagen types I and IV and laminin. This adhesion is essential for maintaining tissue architecture and enabling cells to anchor themselves within tissues.
• ITGA1 also facilitates cell migration, particularly during processes such as wound healing, tissue remodeling, and angiogenesis. During migration, cells dynamically regulate their integrin expression and interaction with the ECM, enabling them to traverse tissues.

Signal Transduction:

• ITGA1 is involved in bidirectional signaling across the plasma membrane. Through outside-in signaling, the engagement of ITGA1 with the ECM can activate intracellular pathways that regulate cytoskeletal organization, gene expression, and cell survival.
• Conversely, inside-out signaling involves the modulation of integrin affinity by intracellular signals, allowing cells to regulate their adhesion to the ECM in response to physiological cues. This process is critical during cell movement and immune responses.

Role in Immune Responses:

• ITGA1 is expressed on certain immune cells, such as natural killer (NK) cells and T cells, where it can modulate immune responses, particularly in inflammatory sites. By facilitating immune cell adhesion to collagen, ITGA1 contributes to immune cell trafficking and localization in inflamed tissues.
• Additionally, ITGA1 expression on fibroblasts and smooth muscle cells in inflamed tissues suggests a role in inflammation and tissue repair.

Tissue Remodeling and Wound Healing:

• ITGA1 plays an important role in tissue remodeling by mediating the interaction between cells and the ECM. During processes such as wound healing, ITGA1 expression increases to promote the adhesion and migration of cells, such as fibroblasts and endothelial cells, which are critical for tissue repair and regeneration.
• The α1β1 integrin is also involved in angiogenesis, promoting the growth of new blood vessels in response to tissue injury or hypoxic conditions.

Tumor Progression:

• ITGA1 is involved in the regulation of tumor cell adhesion, invasion, and metastasis. By interacting with the ECM, cancer cells expressing high levels of ITGA1 can facilitate their attachment to collagen-rich matrices, enabling their spread to distant sites in the body.
• Increased expression of ITGA1 has been associated with tumorigenesis and the development of aggressive cancer phenotypes in certain cancers, including breast cancer, melanoma, and renal cell carcinoma.

Clinical Issues

Cancer:

• The role of ITGA1 in tumor biology has garnered significant interest, as it contributes to tumor growth, invasion, and metastasis. Overexpression of ITGA1 in cancer cells enhances their ability to bind to collagen-rich environments, promoting tumor cell survival and metastasis. As a result, ITGA1 is considered a potential target for anticancer therapies.
• Additionally, ITGA1 may play a role in the tumor microenvironment, where it facilitates interactions between cancer cells and surrounding stromal cells, promoting tumor progression.

Fibrosis:

• ITGA1 has been implicated in fibrotic diseases, where excessive ECM deposition leads to tissue scarring. Increased expression of ITGA1 in fibroblasts and smooth muscle cells can contribute to the development of fibrosis in organs such as the lungs, liver, and kidneys.
• Targeting ITGA1 may offer therapeutic potential for treating fibrotic conditions, as it plays a key role in regulating collagen deposition and tissue remodeling.

Cardiovascular Diseases:

• The role of ITGA1 in regulating vascular remodeling and angiogenesis suggests that it may contribute to cardiovascular diseases, such as atherosclerosis and hypertension. ITGA1 is expressed in vascular smooth muscle cells and endothelial cells, where it influences their behavior during vascular injury and repair.
• Inhibition of ITGA1 function may be beneficial in preventing vascular complications and promoting vascular homeostasis.

Summary

Integrin subunit alpha 1 (ITGA1) is a key transmembrane protein that functions as part of the α1β1 integrin heterodimer, primarily mediating interactions between cells and collagen-rich extracellular matrix. It is involved in crucial physiological processes such as cell adhesion, migration, wound healing, angiogenesis, and immune responses. ITGA1 is also implicated in tumor progression, fibrosis, and cardiovascular diseases, making it an attractive target for therapeutic interventions. Understanding its structure, which includes an extracellular domain responsible for collagen binding, a transmembrane domain for anchoring, and a cytoplasmic domain for signal transduction, provides insights into its diverse functional roles and its significance in both normal and pathological conditions.