Integrin beta-1 (ITGB1), also known as CD29, is a
cell surface receptor
Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral m ...
that in humans is encoded by the ''ITGB1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
This
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 signals such as regulation of the cell cycle, ...
associates with
integrin alpha 1 and
integrin alpha 2 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
Netrin-1 is a protein that in humans is encoded by the ''NTN1'' gene.
Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon gu ...
and
reelin
Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this import ...
. 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
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
. In
cardiac muscle
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...
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
costamere
The costamere is a structural-functional component of striated muscle cells which connects the sarcomere of the muscle to the cell membrane (i.e. the sarcolemma).20: 2327-2331
Costameres are sub-sarcolemmal protein assemblies circumferentially a ...
s, where it aids in the lateral force transmission from the
Z-discs to the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
. Abnormal levels of integrin beta-1D have been found in
limb girdle muscular dystrophy and
polyneuropathy.
Structure
Integrin beta-1 can exist as different
isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
s 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
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 ...
variants have been found for this gene which encode five proteins with alternate
C-termini. 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
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
.
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
In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. This involves coagulation, whi ...
, tissue repair,
immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
and metastatic diffusion of tumor cells.
Integrins link the
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
with the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
and they transmit signals bidirectionally between the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
and
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
ic domains.
Beta-integrins are primarily responsible for targeting integrin dimers to the appropriate subcellular locations, which in adhesive cells is mainly
focal adhesion
In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More ...
s.
Integrin beta-1 mutants lose the ability to target to sites of
focal adhesion
In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More ...
s.
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 acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s of the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
ic domain in exon 6 are retained and then succeeded by a 12
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
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
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
appears to act as a dominant negative in that it inhibits cell adhesion. A second integrin beta-1
isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
, termed beta-1C, was described to have an additional 48
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s appended to the 26
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s in the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
ic domain; the function of this isoform was an inhibitory one on
DNA synthesis
DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. DNA is a macromolecule made up of nucleotide units, which are linked by covalent bonds and hydrogen bonds, in a repeating structure. DNA synthesis occur ...
in the
G1 phase
The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps lead ...
of the
cell cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
. The third
isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
, termed beta-1D, is a
striated muscle
Striations means a series of ridges, furrows or linear marks, and is used in several ways:
* Glacial striation
* Striation (fatigue), in material
* Striation (geology), a ''striation'' as a result of a geological fault
* Striation Valley, in Ant ...
-specific isoform, which replaces the canonical beta-1A
isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
in
cardiac
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
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
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
is produced from splicing into a novel additional exon between exons 6 and 7. The
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
ic domain of integrin beta-1D replaces the distal 21
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s (present in integrin beta-1A) with an alternative stretch of 24
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s (13 unique).
Integrin beta-1D appears to be developmentally regulated during myofibrilogenesis,
appearing immediately following the fusion of
myoblast
Myogenesis is the formation of skeletal muscular tissue, particularly during embryonic development.
Muscle fibers generally form through the fusion of precursor myoblasts into multinucleated fibers called ''myotubes''. In the early development o ...
s in
C2C12
C2C12 is an immortalized mouse myoblast cell line. The C2C12 cell line is a subclone of myoblasts that were originally obtained by Yaffe and Saxel at the Weizmann Institute of Science in Israel in 1977. Developed for ''in vitro'' studies of myo ...
cell with rising levels throughout
myofibril
A myofibril (also known as a muscle fibril or sarcostyle) is a basic rod-like organelle of a muscle cell. Skeletal muscles are composed of long, tubular cells known as muscle fibers, and these cells contain many chains of myofibrils. Each myo ...
lar differentiation.
Integrin beta-1D is specifically localized to
costamere
The costamere is a structural-functional component of striated muscle cells which connects the sarcomere of the muscle to the cell membrane (i.e. the sarcolemma).20: 2327-2331
Costameres are sub-sarcolemmal protein assemblies circumferentially a ...
s and
intercalated disc
Intercalated discs or lines of Eberth are microscopic identifying features of cardiac muscle. Cardiac muscle consists of individual heart muscle cells (cardiomyocytes) connected by intercalated discs to work as a single functional syncytium. By con ...
s of
cardiac muscle
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...
and
costamere
The costamere is a structural-functional component of striated muscle cells which connects the sarcomere of the muscle to the cell membrane (i.e. the sarcolemma).20: 2327-2331
Costameres are sub-sarcolemmal protein assemblies circumferentially a ...
s,
myotendinous junction
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 muscle ...
s 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 resulted in
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
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 activation.
Clinical significance
In patients with
limb girdle muscular dystrophy, 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, levels of
integrin alpha-7B, integrin beta-1D and
agrin
Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. ...
were significantly reduced nearly to undetectable levels; and this corresponded with lower
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
levels.
Interactions
CD29 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
*
ACTN1
Alpha-actinin-1 is a protein that in humans is encoded by the ''ACTN1'' gene.
Function
Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins an ...
;
*
CD46
CD46 complement regulatory protein also known as CD46 (cluster of differentiation 46) and Membrane Cofactor Protein is a protein which in humans is encoded by the ''CD46'' gene. CD46 is an inhibitory complement receptor.
Gene
This gene is fou ...
,
*
CD9
CD9 is a gene encoding a protein that is a member of the transmembrane 4 superfamily also known as the tetraspanin family. It is a cell surface glycoprotein that consists of four transmembrane regions and has two extracellular loops that contain ...
,
*
FHL2
Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the ''FHL2'' gene. LIM proteins contain a highly conserved double zinc finger motif called the LIM domain.
Function
FHL-2 is thought to have ...
,
*
Filamin Filamins are a class of proteins that hold two actin filaments at large angles. Filamin protein in mammals is made up of an actin-binding domain at its N-terminus that is followed by 24 immunoglobulin-like repeat modules of roughly 95 amino acids. ...
,
*
FLNB
Filamin B, beta (FLNB), also known as Filamin B, beta (truncated actin binding protein 278 homolog), is a cytoplasmic protein which in humans is encoded by the ''FLNB'' gene.
FLNB regulates intracellular communication and signalling by cross-linki ...
,
*
CD81,
* GNB2L1
Receptor for activated C kinase 1 (RACK1), also known as guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1), is a 35 kDa protein that in humans is encoded by the RACK1 gene.
Function
RACK1 was originally isolated and identified a ...
,
* ITGB1BP1
Integrin beta-1-binding protein 1 is a protein that in humans is encoded by the ''ITGB1BP1'' gene.
The cytoplasmic domains of integrins are essential for cell adhesion. The protein encoded by this gene binds to the beta1 integrin cytoplasmic domai ...
,
* LGALS8
Galectin-8 is a protein of the galectin family that in humans is encoded by the ''LGALS8'' gene.
Function
This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate rec ...
,
* MAP4K4
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) – also known as hepatocyte progenitor kinase-like/germinal center kinase-like kinase (HGK) and Nck-interacting kinase (NIK) – is an enzyme, specifically a serine/threonine (S/T) ...
,
* NME1
Nucleoside diphosphate kinase A is an enzyme that in humans is encoded by the ''NME1'' gene. It is thought to be a metastasis suppressor.
Function
This gene (NME1) was identified because of its reduced mRNA transcript levels in highly metasta ...
,
* PKC alpha
Protein kinase C alpha (PKCα) is an enzyme that in humans is encoded by the ''PRKCA'' gene.
Function
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messeng ...
,
* TLN1
Talin-1 is a protein that in humans is encoded by the ''TLN1'' gene. Talin-1 is ubiquitously expressed, and is localized to costamere structures in cardiac and skeletal muscle cells, and to focal adhesions in smooth muscle and non-muscle cells. Tal ...
,
* TSPAN4
Tetraspanin-4 is a protein that in humans is encoded by the ''TSPAN4'' gene.
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins th ...
, and
* YWHAB
14-3-3 protein beta/alpha is a protein that in humans is encoded by the ''YWHAB'' gene.
Function
This gene encodes a protein belonging to the 14-3-3 family of proteins, members of which mediate signal transduction by binding to phosphoserine-c ...
.
References
Further reading
*
*
*
External links
*
*
{{Integrins
Integrins
Clusters of differentiation