Talin-1 is a
protein that in humans is encoded by the TLN1gene.[5][6] 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. Talin-1 functions to mediate cell-cell adhesion via the linkage of
integrins to the
actincytoskeleton and in the activation of
integrins. Altered expression of talin-1 has been observed in patients with
heart failure, however no mutations in TLN1 have been linked with specific diseases.
In undifferentiated cultures of myoblasts, talin-1 expression is perinuclear, and then progresses to a cytoplasmic distribution followed by a
sarcomlemmal,
costameric-like pattern by day 15 of differentiation.[37] Homozygous disruption of TLN1 in mice is embryonic lethal, demonstrating that talin-1 is required for normal
embryogenesis.[38] It has been shown, however, that talin-1 expression is minor in adult
cardiomyocytes, and becomes more prominent at
costameres during
cardiac hypertrophy induced by pharmacological and mechanical stress.[39]
The primary function of talin-1 involves the linkage of integrins to the actin cytoskeleton and in the energy-dependent activation of integrins.[9][40] Functions for talin-1 in specific tissues have been illuminated through conditional knockout animals. Studies employing the conditional knockout of talin 1 in
skeletal muscle have demonstrated its role in maintaining
integrin attachment sites at
myotendinous junctions; knockout mice develop progressive
myopathy and show deficits in muscle force generation.[41] In
platelets, conditional knockout of talin-1 results in the inability to activate
integrins in response to
plateletagonists, resulting in mice with severe hemostatic defects and resistance to arterial
thrombosis.[42] Conditional knockout of talin-1 in
cardiomyocytes shows that mice have normal cardiac function at baseline, but improved function, blunted hypertrophy, and attenuated fibrosis when subjected to pressure overload-induced
cardiac hypertrophy, which correlated with blunted
ERK1/2,
p38,
Akt, and
glycogen synthase kinase 3 responses. These data suggest that upregulation of talin-1 in
cardiac hypertrophy may be detrimental to
cardiomyocytes function.[39]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Gilmore AP, Ohanian V, Spurr NK, Critchley DR (Aug 1995). "Localisation of the human gene encoding the cytoskeletal protein talin to chromosome 9p". Human Genetics. 96 (2): 221–4.
doi:
10.1007/BF00207384.
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^Dietrich C, Goldmann WH, Sackmann E, Isenberg G (Jun 1993). "Interaction of NBD-talin with lipid monolayers. A film balance study". FEBS Letters. 324 (1): 37–40.
doi:
10.1016/0014-5793(93)81527-7.
PMID8504857.
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^Goldmann WH, Niggli V, Kaufmann S, Isenberg G (Aug 1992). "Probing actin and liposome interaction of talin and talin-vinculin complexes: a kinetic, thermodynamic and lipid labeling study". Biochemistry. 31 (33): 7665–71.
doi:
10.1021/bi00148a030.
PMID1510952.
^Heise H, Bayerl T, Isenberg G, Sackmann E (Jan 1991). "Human platelet P-235, a talin-like actin binding protein, binds selectively to mixed lipid bilayers". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1061 (2): 121–31.
doi:
10.1016/0005-2736(91)90276-e.
PMID1900196.
^Wu JC, Sung HC, Chung TH, DePhilip RM (2002). "Role of N-cadherin- and integrin-based costameres in the development of rat cardiomyocytes". Journal of Cellular Biochemistry. 84 (4): 717–24.
doi:
10.1002/jcb.10092.
PMID11835397.
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^Trimarchi F, Favaloro A, Fulle S, Magaudda L, Puglielli C, Di Mauro D (2006). "Culture of human skeletal muscle myoblasts: timing appearance and localization of dystrophin-glycoprotein complex and vinculin-talin-integrin complex". Cells Tissues Organs. 183 (2): 87–98.
doi:
10.1159/000095513.
PMID17053325.
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^Wegener KL, Basran J, Bagshaw CR, Campbell ID, Roberts GC, Critchley DR, Barsukov IL (Sep 2008). "Structural basis for the interaction between the cytoplasmic domain of the hyaluronate receptor layilin and the talin F3 subdomain". Journal of Molecular Biology. 382 (1): 112–26.
doi:
10.1016/j.jmb.2008.06.087.
PMID18638481.
^Salgia R, Sattler M, Pisick E, Li JL, Griffin JD (Feb 1996). "p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl". Experimental Hematology. 24 (2): 310–3.
PMID8641358.
^Di Paolo G, Pellegrini L, Letinic K, Cestra G, Zoncu R, Voronov S, Chang S, Guo J, Wenk MR, De Camilli P (Nov 2002). "Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin". Nature. 420 (6911): 85–9.
Bibcode:
2002Natur.420...85D.
doi:
10.1038/nature01147.
PMID12422219.
S2CID1746983.
^Sun N, Critchley DR, Paulin D, Li Z, Robson RM (May 2008). "Identification of a repeated domain within mammalian alpha-synemin that interacts directly with talin". Experimental Cell Research. 314 (8): 1839–49.
doi:
10.1016/j.yexcr.2008.01.034.
PMID18342854.