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 integra ...

that in humans is encoded by the ''ITGB1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. This

integrin Integrins are transmembrane receptors that help 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, o ...

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 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 importa ...

. 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 and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

. In

cardiac muscle Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...

and

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

, 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 ...

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 (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

. Abnormal levels of integrin beta-1D have been found in limb girdle muscular dystrophy and

polyneuropathy Polyneuropathy () 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 hands and feet and may prog ...

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 and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

s via

alternative splicing Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...

. Six

alternatively spliced Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...

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 ...

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. Hemostasis involves three ...

, tissue repair,

immune response An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...

and metastatic diffusion of tumor cells. Integrins link the

with the

and they transmit signals bidirectionally between the

and

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

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 (biolo ...

s. Integrin beta-1 mutants lose the ability to target to sites of

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 over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s of the

ic domain in exon 6 are retained and then succeeded by a 12

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., gen ...

ic region. The integrin beta-1B

appears to act as a dominant negative in that it inhibits cell adhesion. A second integrin beta-1

, termed beta-1C, was described to have an additional 48

s appended to the 26

s in the

ic domain; the function of this isoform was an inhibitory one on DNA synthesis 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 Messenger RNA, mRNA and proteins in preparation for subsequ ...

of the

cell cycle The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...

. The third

, termed beta-1D, is a

striated muscle Striated muscle tissue is a muscle tissue that features repeating functional units called sarcomeres. Under the microscope, sarcomeres are visible along muscle fibers, giving a striated appearance to the tissue. The two types of striated muscle a ...

-specific isoform, which replaces the canonical beta-1A

cardiac The heart is a muscular organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrients to the tissu ...

and

cells. This

is produced from splicing into a novel additional exon between exons 6 and 7. The

ic domain of integrin beta-1D replaces the distal 21

s (present in integrin beta-1A) with an alternative stretch of 24

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 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 Skeletal muscle#Skeletal muscle cells, muscle fibers, and these cells contain ...

lar differentiation. Integrin beta-1D is specifically localized to

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#Cardia ...

s of

and

s, 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

, 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 conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

of pp125FAK and induced

mitogen-activated protein kinase A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of serine/threonine-specific protein kinases involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflamma ...

activation.

Clinical significance

In patients with limb girdle muscular dystrophy, type 2C, beta-1D integrin has been shown to be severely reduced in

biopsies, coordinate with a reduction in alpha 7B-integrin and filamin 2. In patients with sensitive-motor

, 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 synaptogenesi ...

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 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 cytoskeleton, cytoskeletal proteins, including the alpha and bet ...

; * CD46, * CD9, * FHL2, *

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, *

CD81 CD81 molecule, also known as CD81 (Cluster of Differentiation 81), is a protein which in humans is encoded by the ''CD81'' gene. It is also known as 26 kDa cell surface protein, TAPA-1 (Target of the Antiproliferative Antibody 1), and Tetraspanin- ...

, * GNB2L1, *

ITGB1BP1 Integrin beta-1-binding protein 1 is a protein that in humans is encoded by the ''ITGB1BP1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in ...

, * LGALS8, * MAP4K4, * NME1, *

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, * TSPAN4, 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 ...

References

External links