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Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ''ITGB1'' gene. This integrin associates with
integrin alpha 1 Integrin alpha-1 also CD49a is an integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular ...
and
integrin alpha 2 Integrin alpha-2, or CD49b (cluster of differentiation 49b), is a protein which in humans is encoded by the ''CD49b'' gene. The CD49b protein is an integrin alpha subunit. It makes up half of the α2β1 integrin duplex. Integrins are heterodim ...
to form integrin complexes which function as
collagen receptor Collagen receptors are membrane proteins that bind the extracellular matrix protein collagen, the most abundant protein in mammals. They control mainly cell proliferation, migration and adhesion, coagulation cascade activation and they affect ECM s ...
s. It also forms dimers with integrin alpha 3 to form integrin receptors for netrin 1 and reelin. These and other integrin beta 1 complexes have been historically known as very late activation (VLA) antigens. Integrin beta 1 is expressed as at least four different isoforms. In cardiac muscle and
skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
, the integrin beta-1D isoform is specifically expressed, and localizes to costameres, where it aids in the lateral force transmission from the Z-discs to the extracellular matrix. Abnormal levels of integrin beta-1D have been found in
limb girdle muscular dystrophy Limb may refer to: Science and technology *Limb (anatomy), an appendage of a human or animal *Limb, a large or main branch of a tree *Limb, in astronomy, the curved edge of the apparent disk of a celestial body, e.g. lunar limb *Limb, in botany, ...
and
polyneuropathy Polyneuropathy ( poly- + neuro- + -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hand ...
.


Structure

Integrin beta-1 can exist as different isoforms via
alternative splicing Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
. Six alternatively spliced variants have been found for this gene which encode five proteins with alternate
C-termini The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
. Integrin receptors exist as heterodimers, and greater than 20 different integrin heterodimeric receptors have been described. All integrins, alpha and beta forms, have large extracellular and short intracellular domains. The cytoplasmic domain of integrin beta-1 binds to the actin cytoskeleton. Integrin beta-1 is the most abundant beta-integrin expressed and associates with at least 10 different integrin-alpha subunits.


Function

Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. Integrins link the actin cytoskeleton with the extracellular matrix and they transmit signals bidirectionally between the extracellular matrix and cytoplasmic domains. Beta-integrins are primarily responsible for targeting integrin dimers to the appropriate subcellular locations, which in adhesive cells is mainly focal adhesions. Integrin beta-1 mutants lose the ability to target to sites of focal adhesions. Three novel isoforms of integrin beta-1 have been identified, termed beta-1B, beta-1C and beta-1D. Integrin beta-1B is transcribed when the proximal 26 amino acids of the cytoplasmic domain in exon 6 are retained and then succeeded by a 12 amino acid stretch from an adjacent
intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...
ic region. The integrin beta-1B isoform appears to act as a dominant negative in that it inhibits cell adhesion. A second integrin beta-1 isoform, termed beta-1C, was described to have an additional 48 amino acids appended to the 26 amino acids in the cytoplasmic domain; the function of this isoform was an inhibitory one on DNA synthesis in the G1 phase of the cell cycle. The third isoform, termed beta-1D, is a striated muscle-specific isoform, which replaces the canonical beta-1A isoform in cardiac and
skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
cells. This isoform is produced from splicing into a novel additional exon between exons 6 and 7. The cytoplasmic domain of integrin beta-1D replaces the distal 21 amino acids (present in integrin beta-1A) with an alternative stretch of 24 amino acids (13 unique). Integrin beta-1D appears to be developmentally regulated during myofibrilogenesis, appearing immediately following the fusion of myoblasts in C2C12 cell with rising levels throughout myofibrillar differentiation. Integrin beta-1D is specifically localized to costameres and intercalated discs of cardiac muscle and costameres, myotendinous junctions and
neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...
s of
skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
, and it appears to function in general like other integrins, as the clustering of beta-1D integrins on the surface of
CHO cells Chinese hamster ovary (CHO) cells are an epithelial cell line derived from the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therapeutic proteins. They have foun ...
resulted in tyrosine
phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
of pp125FAK and induced
mitogen-activated protein kinase A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses to ...
activation.


Clinical significance

In patients with
limb girdle muscular dystrophy Limb may refer to: Science and technology *Limb (anatomy), an appendage of a human or animal *Limb, a large or main branch of a tree *Limb, in astronomy, the curved edge of the apparent disk of a celestial body, e.g. lunar limb *Limb, in botany, ...
, type 2C, beta-1D integrin has been shown to be severely reduced in
skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
biopsies, coordinate with a reduction in alpha 7B-integrin and filamin 2. In patients with sensitive-motor
polyneuropathy Polyneuropathy ( poly- + neuro- + -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hand ...
, levels of integrin alpha-7B, integrin beta-1D and agrin were significantly reduced nearly to undetectable levels; and this corresponded with lower mRNA levels.


Interactions

CD29 has been shown to interact with * ACTN1; * CD46, * CD9, * FHL2, * Filamin, * FLNB, * CD81, * GNB2L1, * ITGB1BP1, * LGALS8, * MAP4K4, * NME1, * PKC alpha, * TLN1, * TSPAN4, and * YWHAB.


References


Further reading

* * *


External links

* * {{Integrins Integrins Clusters of differentiation