Talin-1 is aprotein that in humans is encoded by theTLN1gene.[5][6] Talin-1 is ubiquitously expressed, and is localized tocostamere structures incardiac andskeletal muscle cells, and tofocal adhesions insmooth muscle and non-muscle cells. Talin-1 functions to mediate cell-cell adhesion via the linkage ofintegrins to theactincytoskeleton and in the activation ofintegrins. Altered expression of talin-1 has been observed in patients withheart failure, however no mutations inTLN1 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 asarcomlemmal,costameric-like pattern by day 15 of differentiation.[37] Homozygous disruption ofTLN1 in mice is embryonic lethal, demonstrating that talin-1 is required for normalembryogenesis.[38] It has been shown, however, that talin-1 expression is minor in adultcardiomyocytes, and becomes more prominent atcostameres duringcardiac 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 inskeletal muscle have demonstrated its role in maintainingintegrin attachment sites atmyotendinous junctions; knockout mice develop progressivemyopathy and show deficits in muscle force generation.[41] Inplatelets, conditional knockout of talin-1 results in the inability to activateintegrins in response toplateletagonists, resulting in mice with severe hemostatic defects and resistance to arterialthrombosis.[42] Conditional knockout of talin-1 incardiomyocytes shows that mice have normal cardiac function at baseline, but improved function, blunted hypertrophy, and attenuated fibrosis when subjected to pressure overload-inducedcardiac hypertrophy, which correlated with bluntedERK1/2,p38,Akt, andglycogen synthase kinase 3 responses. These data suggest that upregulation of talin-1 incardiac hypertrophy may be detrimental tocardiomyocytes 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.PMID7635475.S2CID38856479.
^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.S2CID28938842.
^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.S2CID23553678.
^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.
