ITGB1 - integrin subunit beta 1 |Elisa - Clia - Antibody - Protein

Background

ITGB1, also known as integrin subunit beta 1 or CD29, is a crucial component of integrins, a large family of cell adhesion molecules involved in mediating interactions between cells and the extracellular matrix (ECM). Integrins play a vital role in various cellular processes, including cell adhesion, migration, proliferation, and differentiation. ITGB1, in particular, is an essential β subunit that pairs with multiple α subunits to form a variety of heterodimeric integrins. These integrins facilitate the binding of cells to ECM proteins, such as fibronectin, collagen, and laminin, and are critical for tissue integrity, wound healing, and development.

ITGB1 is ubiquitously expressed across many cell types and tissues, including fibroblasts, endothelial cells, epithelial cells, and immune cells, reflecting its broad role in cellular homeostasis and signaling. Its function extends beyond simple adhesion, as ITGB1 integrins are involved in transmitting signals bidirectionally across the cell membrane, influencing cellular behavior based on external cues. Through a process called "outside-in" and "inside-out" signaling, ITGB1 integrins regulate cell motility, polarity, and survival, contributing to embryogenesis, immune responses, and cancer progression.

Protein Structure

The ITGB1 protein consists of 798 amino acids and is a single-pass transmembrane glycoprotein that forms part of the integrin receptor complex. The structure of ITGB1 can be divided into three key domains:

Extracellular Domain:

• The extracellular domain of ITGB1 spans approximately 700 amino acids and is responsible for mediating ligand binding when paired with an α subunit. This domain contains several cysteine-rich repeats and calcium-binding motifs, which are crucial for integrin activation and conformational changes required for ligand engagement.
• This domain undergoes major conformational shifts between a bent, inactive state and an extended, active state. When integrins are in the bent state, ligand binding is prevented, but upon cellular signals or external stimuli, ITGB1 extends to interact with ECM ligands, facilitating cell adhesion and downstream signaling.
• Ligands that bind to ITGB1-containing integrins include fibronectin, laminin, collagen, and vitronectin, highlighting its role in interacting with diverse matrix proteins.

Transmembrane Domain:

• The transmembrane domain consists of a single hydrophobic α-helix of 20-25 amino acids that anchors ITGB1 into the plasma membrane. This domain plays a key role in transmitting signals from the extracellular matrix to the intracellular signaling machinery. The transmembrane helices of ITGB1 interact with the α subunit to maintain the integrin in its inactive state and undergo structural rearrangements upon activation.

Cytoplasmic Domain:

• The cytoplasmic tail of ITGB1 is relatively short (~47 amino acids) but is highly significant for intracellular signaling. It interacts with various cytoskeletal proteins and signaling molecules, such as talin, kindlin, and paxillin, that link integrins to the actin cytoskeleton. These interactions are critical for integrin-mediated signal transduction, particularly for cell spreading, focal adhesion formation, and cell migration.
• The cytoplasmic domain is also essential for "inside-out" signaling, a process by which intracellular signals regulate the affinity of ITGB1 for its ligands, controlling cellular adhesion in response to physiological stimuli.

Classification and Subtypes

ITGB1 is part of the integrin β-subunit family, which pairs with various α-subunits to form distinct heterodimeric integrins. ITGB1 can associate with 12 different α subunits, forming at least 12 distinct integrin heterodimers, each with a specific set of ligands and functions. Some of the most well-characterized ITGB1 heterodimers include:

1. α1β1 (VLA-1): Binds to collagen and laminin, involved in tissue remodeling and fibrosis.
2. α2β1 (VLA-2): Binds to collagen and laminin, essential for platelet adhesion and collagen signaling.
3. α3β1 (VLA-3): Binds to fibronectin, laminin, and collagen, crucial for epithelial cell adhesion and migration.
4. α4β1 (VLA-4): Binds to VCAM-1 (vascular cell adhesion molecule 1) and fibronectin, important for leukocyte migration and inflammation.
5. α5β1 (VLA-5): Binds primarily to fibronectin, plays a central role in cell migration, proliferation, and survival.
6. α6β1: Binds to laminin, critical for cell adhesion to the basement membrane, involved in tissue architecture and integrity.

Each of these heterodimers mediates distinct functions depending on the ligand, cell type, and environment, highlighting the versatility and functional diversity of ITGB1.

Function and Biological Significance

The primary function of ITGB1 is to mediate cell-matrix interactions by facilitating adhesion between cells and the extracellular matrix. However, ITGB1’s role extends to several critical biological processes:

Cell Adhesion:

• ITGB1 integrins anchor cells to the ECM, maintaining tissue architecture and integrity. In epithelial tissues, ITGB1 is necessary for keeping cells attached to the basement membrane, thereby ensuring proper tissue organization and stability.

Cell Migration:

• ITGB1 is a key player in cell migration, particularly in processes such as wound healing, immune cell trafficking, and cancer metastasis. By interacting with ECM proteins like fibronectin, ITGB1 controls cell movement by orchestrating the formation of focal adhesions and directing cytoskeletal rearrangements.

Cell Proliferation and Survival:

• ITGB1 integrins are involved in regulating cell survival signals through interactions with the ECM and intracellular signaling pathways, such as the PI3K-Akt and MAPK pathways. This regulation is crucial for preventing apoptosis (anoikis) during tissue remodeling or under stress conditions.

Development:

• ITGB1 plays a fundamental role during embryogenesis and organ development. Its role in cell adhesion and migration is essential for tissue patterning, especially in the formation of blood vessels (angiogenesis), the nervous system, and skin development.

Immune Response:

• ITGB1 integrins participate in immune functions by facilitating leukocyte adhesion and migration to sites of inflammation. The α4β1 heterodimer, in particular, mediates the migration of immune cells into tissues during inflammation, making ITGB1 crucial for immune surveillance and responses.

Signal Transduction:

• ITGB1 mediates bidirectional signaling, meaning it can transmit signals from the ECM to the cell’s interior (outside-in signaling) and from the cytoplasm to the ECM (inside-out signaling). This signaling is essential for dynamically regulating adhesion, motility, and cell fate based on environmental cues.

Clinical Issues

Given the wide range of functions ITGB1 plays in cell behavior, its dysregulation is implicated in various clinical conditions, particularly in cancer, fibrosis, and immune-related diseases.

Cancer:

• ITGB1 is frequently overexpressed in various cancers, including breast cancer, lung cancer, and melanoma. ITGB1 promotes tumor progression by enhancing cancer cell adhesion to the ECM, facilitating metastasis, and promoting resistance to apoptosis. Elevated ITGB1 expression is often associated with poor prognosis, as it supports the invasive and metastatic behavior of tumor cells.

Fibrosis:

• In fibrotic diseases, such as liver fibrosis or pulmonary fibrosis, ITGB1-mediated interactions with the ECM contribute to excessive deposition of collagen and other matrix proteins. This leads to tissue stiffness and impaired function, driving the progression of fibrotic conditions.

Autoimmune and Inflammatory Diseases:

• The role of ITGB1 integrins in leukocyte migration makes them significant in inflammatory conditions such as multiple sclerosis (MS) and rheumatoid arthritis (RA). The α4β1 heterodimer is particularly involved in leukocyte trafficking across the endothelium to sites of inflammation, and inhibitors targeting this integrin (e.g., natalizumab) have been developed as therapeutic agents for autoimmune diseases like MS.

Cardiovascular Disease:

• ITGB1’s involvement in angiogenesis and vascular remodeling makes it a contributor to cardiovascular diseases, such as atherosclerosis and restenosis after angioplasty. The integrin’s role in endothelial cell adhesion and migration is critical for the formation of new blood vessels and the maintenance of vascular integrity.

Summary

ITGB1 (integrin subunit beta 1) is a highly versatile and critical protein that forms heterodimers with various α subunits to mediate cell adhesion, migration, proliferation, and survival. It plays a fundamental role in normal physiological processes, such as tissue development, wound healing, and immune responses, while also being implicated in pathological conditions, including cancer metastasis, fibrosis, and inflammatory diseases. The structure of ITGB1, with its extracellular ligand-binding domain, transmembrane helix, and intracellular cytoplasmic tail, is designed for dynamic signaling and functional diversity. Given its broad biological significance, ITGB1 is an important target for therapeutic interventions in diseases characterized by abnormal cell-ECM interactions.