Mammalian protein found in Homo sapiens
Integrin beta-1 (ITGB1 ), also known as CD29 , is a
cell surface receptor that in humans is encoded by the ITGB1
gene .
[5] This
integrin associates with
integrin alpha 1 and
integrin alpha 2 to form integrin complexes which function as
collagen receptors . 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 , 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 and
polyneuropathy .
Structure
Integrin beta-1 can exist as different
isoforms via
alternative splicing . Six
alternatively spliced variants have been found for this gene which encode five proteins with alternate
C-termini .
[6] 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.
[7] The cytoplasmic domain of integrin beta-1 binds to the
actin
cytoskeleton .
[8] Integrin beta-1 is the most abundant beta-integrin expressed and associates with at least 10 different integrin-alpha subunits.
[7]
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 .
[7] Integrins link the
actin
cytoskeleton with the
extracellular matrix and they transmit signals bidirectionally between the
extracellular matrix and
cytoplasmic domains.
[9]
[10]
Beta-integrins are primarily responsible for targeting integrin dimers to the appropriate subcellular locations, which in adhesive cells is mainly
focal adhesions .
[8]
[11] Integrin beta-1 mutants lose the ability to target to sites of
focal adhesions .
[12]
[13]
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
intronic region.
[14] The integrin beta-1B
isoform appears to act as a dominant negative in that it inhibits cell adhesion.
[15] 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;
[16] the function of this isoform was an inhibitory one on
DNA synthesis in the
G1 phase of the
cell cycle .
[17] The third
isoform , termed beta-1D, is a
striated muscle -specific isoform, which replaces the canonical beta-1A
isoform in
cardiac and
skeletal muscle 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).
[18]
[19]
Integrin beta-1D appears to be developmentally regulated during myofibrilogenesis,
[19] appearing immediately following the fusion of
myoblasts in
C2C12 cell with rising levels throughout
myofibrillar differentiation.
[20] Integrin beta-1D is specifically localized to
costameres and
intercalated discs of
cardiac muscle and
costameres ,
myotendinous junctions and
neuromuscular junctions of
skeletal muscle , 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
phosphorylation of
pp125FAK and induced
mitogen-activated protein kinase activation.
[20]
Clinical significance
In patients with
limb girdle muscular dystrophy , type 2C, beta-1D integrin has been shown to be severely reduced in
skeletal muscle biopsies, coordinate with a reduction in
alpha 7B-integrin and
filamin 2 .
[21]
In patients with sensitive-motor
polyneuropathy , levels of
integrin alpha-7B , integrin beta-1D and
agrin were significantly reduced nearly to undetectable levels; and this corresponded with lower
mRNA levels.
[22]
Interactions
CD29 has been shown to
interact with
ACTN1 ;
[23]
[24]
CD46 ,
[25]
CD9 ,
[26]
[27]
FHL2 ,
[28]
Filamin ,
[29]
[30]
FLNB ,
[29]
CD81 ,
[27]
[31]
GNB2L1 ,
[32]
[33]
ITGB1BP1 ,
[34]
[35]
LGALS8 ,
[36]
MAP4K4 ,
[37]
NME1 ,
[38]
PKC alpha ,
[32]
[39]
TLN1 ,
[40]
[41]
TSPAN4 ,
[42] and
YWHAB .
[43]
References
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Further reading
External links
1–50 51–100 101–150 151–200 201–250 251–300 301–350
Alpha Beta Dimers
Cytoadhesin receptor: Fibrinogen receptor: Fibronectin receptor: Leukocyte-adhesion receptor: Very late antigen receptor: Vitronectin receptor: