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