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Adhesome

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Calponin homology (CH) domain, which is an F-actin binding motif; Src homology 2 (SH2) domain, which mediate interaction with phosphorylated tyrosine residues; armadillo (ARM) GUK and LIM domains, which mediate specific protein-protein binding. The literature-based adhesome contains enzymes, such as protein tyrosine and serine/threonine kinases and phosphatases, guanine nucleotide exchange factors and GTPase activating proteins, E3-ligases and proteases, that regulate adhesion through
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While proteomic methods identified many novel proteins that potentially might be adhesome components they cannot be regarded as adhesome components until they are validated to fulfill the following criteria: 1. they localize to a cell adhesion structure such as focal adhesion or adherens junction. 2.
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Mass spectrometry has been successfully used to identify changes in the composition of the adhesome upon perturbation. Schiller et al. as well as Kuo et al. examined the effect of inhibition of myosin contractility on the integrin adhesome composition and found LIM domain proteins and beta-PIX to be
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receptors and therefore the adhesome of cell-cell adhesion is referred to as the cadherin adhesome or cadhesome. The first attempts to establish the set of proteins that participate directly ('bona fide' adhesome components) or affect indirectly ('associated' adhesome components) cell adhesion were
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tension sensitive. Gou et al. found little change in the cadherin adhesome after calcium depletion from the media, which essentially abrogates cell-cell adhesion. Reinhard Fassler and co-workers used proteomics on specifically engineered cell lines to distinguish between the adhesome of β1- and
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from the unicellular relatives of animals through simple animals (e.g. sponges) to mammals. Surprisingly, the majority of cadherin adhesome proteins existed long before multicellularity and had other functions in cells. Later, with the emergence of the cadherin-catenin-actin structure they were
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of the many structural and scaffolding proteins found in the adhesome. The proteomic-based studies have identified many proteins from functional groups that haven't previously been associated with cell adhesion sites, such as proteins involved in RNA splicing, translation, trafficking, golgi,
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The adhesome contains multi domain proteins with various functions, some of which are specifically enriched in the adhesome compared to the cell proteome. Protein domains enriched in the adhesome include: Pleckstrin homology (PH) and FERM domains, which target proteins to the plasma membrane;
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Schiller, Herbert B.; Hermann, Michaela-Rosemarie; Polleux, Julien; Vignaud, Timothée; Zanivan, Sara; Friedel, Caroline C.; Sun, Zhiqi; Raducanu, Aurelia; Gottschalk, Kay-E. (2013). "β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based
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to describe the complement of cell-cell and cell-matrix adhesion receptors in an organism and later expanded by Benny Geiger and co-workers to include the entire network of structural and signaling proteins involved in regulating cell-matrix adhesion.
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have detected hundreds more proteins associated with integrin adhesions. However, a comparison of multiple proteomic studies of the integrin adhesome of fibroblasts attached to fibronectin found only 60 proteins common to all studies.
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Cell-matrix adhesions have been more extensively investigated by proteomics compared with cell-cell adhesions because they are more readily isolated from cells attached to glass. The advent of
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endoplasmic reticulum, and metabolic enzymes. Whether these proteins are indeed an integral part of the adhesome or an artifact of the proteomic methods remains to be seen.
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Horton, Edward R.; Byron, Adam; Askari, Janet A.; Ng, Daniel H. J.; Millon-Frémillon, Angélique; Robertson, Joseph; Koper, Ewa J.; Paul, Nikki R.; Warwood, Stacey (2015).
807:"Biotin ligase tagging identifies proteins proximal to E-cadherin, including lipoma preferred partner, a regulator of epithelial cell–cell and cell–substrate adhesion" 674: 80:
they directly interact with one of the core adhesome components, such as integrin, cadherin or catenins AND/OR their knockdown has a clear effect on cell adhesion.
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Byron, Adam; Humphries, Jonathan D.; Bass, Mark D.; Knight, David; Humphries, Martin J. (2011-04-05). "Proteomic Analysis of Integrin Adhesion Complexes".
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Winograd-Katz, Sabina E.; Fässler, Reinhard; Geiger, Benjamin; Legate, Kyle R. (2014). "The integrin adhesome: from genes and proteins to human disease".
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based on mining of the primary research literature, and resulted in approximately 200 protein in either integrin or cadherin adhesomes. Later, unbiased
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Itallie, Christina M. Van; Tietgens, Amber Jean; Aponte, Angel; Fredriksson, Karin; Fanning, Alan S.; Gucek, Marjan; Anderson, James M. (2014-02-15).
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Padmanabhan, Anup; Rao, Megha Vaman; Wu, Yao; Zaidel-Bar, Ronen (2015). "Jack of all trades: functional modularity in the adherens junction".
640: 527:"Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation" 137:
Whittaker, Charles A.; Bergeron, Karl-Frederik; Whittle, James; Brandhorst, Bruce P.; Burke, Robert D.; Hynes, Richard O. (December 2006).
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and therefore the adhesome of cell-matrix adhesion is referred to as the integrin adhesome. Cell-cell adhesion is primarily mediated by
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The availability of genomes of many organisms on the tree of life has opened up the possibility to study how the adhesome
576:"Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly" 748:
Guo, Zhenhuan; Neilson, Lisa J.; Zhong, Hang; Murray, Paul S.; Zanivan, Sara; Zaidel-Bar, Ronen (2014-12-02).
1086: 690:"A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells" 1081: 888: 668: 452: 325: 68: 1057: 1022: 1004: 962: 944: 880: 844: 826: 787: 769: 727: 709: 656: 636: 605: 556: 525:
Kuo, Jean-Cheng; Han, Xuemei; Hsiao, Cheng-Te; III, John R. Yates; Waterman, Clare M. (2011).
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Zaidel-Bar, Ronen; Itzkovitz, Shalev; Ma'ayan, Avi; Iyengar, Ravi; Geiger, Benjamin (2007).
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Kuo, J. C.; Han, X.; Yates Jr, 3rd; Waterman, C. M. (2012-01-01). Shimaoka, Motomu (ed.).
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Isolation of Focal Adhesion Proteins for Biochemical and Proteomic Analysis - Springer
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by birA* has facilitated the first proteomics-based studies of the cadherin adhesome.
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Humphries and co-workers named these 60 proteins the 'consensus integrin adhesome'.
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Systems Biomedicine: Concepts and Perspectives ed. E.T. Liu and D.A. Lauffenburger
632: 154: 627:. Methods in Molecular Biology. Vol. 757. Humana Press. pp. 297–323. 1053: 765: 432: 43: 1008: 948: 830: 773: 713: 440: 373: 263: 116: 34: 1061: 1026: 966: 884: 848: 791: 731: 660: 609: 560: 508: 448: 381: 321: 281: 221: 172: 940: 705: 490: 1000: 38: 475:"Mechanosensitivity and compositional dynamics of cell–matrix adhesions" 203: 822: 688:
Roux, Kyle J.; Kim, Dae In; Raida, Manfred; Burke, Brian (2012-03-19).
364: 347: 255: 876: 591: 542: 313: 985:"Pre-metazoan origins and evolution of the cadherin adhesome" 395: 473:
Schiller, Herbert B; Fässler, Reinhard (2013-06-01).
925:"Evolution of complexity in the integrin adhesome" 238:Zaidel-Bar, Ronen; Geiger, Benjamin (2010-05-01). 983:Murray, Paul S.; Zaidel-Bar, Ronen (2014-12-15). 912:. Oxford: Academic Press. 2009. pp. 139–152. 743: 741: 33:The major cell-matrix adhesion receptors are 8: 673:: CS1 maint: numeric names: authors list ( 188:"Functional atlas of the integrin adhesome" 1016: 956: 838: 781: 721: 650: 599: 550: 498: 363: 271: 211: 162: 129: 666: 978: 976: 904: 902: 302:Nature Reviews Molecular Cell Biology 7: 520: 518: 468: 466: 341: 339: 295: 293: 291: 233: 231: 240:"The switchable integrin adhesome" 14: 923:Zaidel-Bar, Ronen (2009-08-10). 346:Zaidel-Bar, Ronen (2013-01-15). 1042:Current Opinion in Cell Biology 396:"Adhesome- Project Description" 348:"Cadherin adhesome at a glance" 104:post translational modification 1: 120:co-opted into the cadhesome. 633:10.1007/978-1-61779-166-6_19 929:The Journal of Cell Biology 694:The Journal of Cell Biology 155:10.1016/j.ydbio.2006.07.044 1103: 1054:10.1016/j.ceb.2015.06.008 766:10.1126/scisignal.2005473 433:10.1126/scisignal.2001827 139:"The echinoderm adhesome" 69:proximity biotinylation 941:10.1083/jcb.200811067 706:10.1083/jcb.201112098 491:10.1038/embor.2013.49 143:Developmental Biology 97:Multi domain proteins 46:approaches utilizing 1001:10.1242/bio.20149761 863:microenvironments". 865:Nature Cell Biology 580:Nature Cell Biology 531:Nature Cell Biology 204:10.1038/ncb0807-858 192:Nature Cell Biology 823:10.1242/jcs.140475 365:10.1242/jcs.111559 256:10.1242/jcs.066183 91:αv-class integrins 20:was first used by 995:(12): 1183–1195. 642:978-1-61779-165-9 586:(12): 1577–1587. 84:Mass spectrometry 48:mass spectrometry 1094: 1066: 1065: 1037: 1031: 1030: 1020: 980: 971: 970: 960: 920: 914: 913: 906: 897: 896: 859: 853: 852: 842: 802: 796: 795: 785: 745: 736: 735: 725: 685: 679: 678: 672: 664: 654: 620: 614: 613: 603: 571: 565: 564: 554: 522: 513: 512: 502: 470: 461: 460: 416: 410: 409: 407: 406: 400:www.adhesome.org 392: 386: 385: 367: 343: 334: 333: 297: 286: 285: 275: 250:(9): 1385–1388. 235: 226: 225: 215: 183: 177: 176: 166: 134: 1102: 1101: 1097: 1096: 1095: 1093: 1092: 1091: 1072: 1071: 1070: 1069: 1039: 1038: 1034: 982: 981: 974: 922: 921: 917: 908: 907: 900: 877:10.1038/ncb2747 861: 860: 856: 804: 803: 799: 747: 746: 739: 687: 686: 682: 665: 643: 622: 621: 617: 592:10.1038/ncb3257 573: 572: 568: 543:10.1038/ncb2216 524: 523: 516: 472: 471: 464: 418: 417: 413: 404: 402: 394: 393: 389: 345: 344: 337: 314:10.1038/nrm3769 299: 298: 289: 237: 236: 229: 185: 184: 180: 136: 135: 131: 126: 113: 99: 86: 77: 65: 57: 31: 12: 11: 5: 1100: 1098: 1090: 1089: 1087:Cell signaling 1084: 1074: 1073: 1068: 1067: 1032: 972: 935:(3): 317–321. 915: 898: 871:(6): 625–636. 854: 817:(4): 885–895. 797: 737: 700:(6): 801–810. 680: 641: 615: 566: 537:(4): 383–393. 514: 485:(6): 509–519. 462: 411: 387: 358:(2): 373–378. 335: 308:(4): 273–288. 287: 227: 198:(8): 858–867. 178: 149:(1): 252–266. 128: 127: 125: 122: 112: 109: 98: 95: 85: 82: 76: 73: 64: 61: 56: 53: 30: 27: 13: 10: 9: 6: 4: 3: 2: 1099: 1088: 1085: 1083: 1080: 1079: 1077: 1063: 1059: 1055: 1051: 1047: 1043: 1036: 1033: 1028: 1024: 1019: 1014: 1010: 1006: 1002: 998: 994: 990: 986: 979: 977: 973: 968: 964: 959: 954: 950: 946: 942: 938: 934: 930: 926: 919: 916: 911: 905: 903: 899: 894: 890: 886: 882: 878: 874: 870: 866: 858: 855: 850: 846: 841: 836: 832: 828: 824: 820: 816: 812: 808: 801: 798: 793: 789: 784: 779: 775: 771: 767: 763: 759: 755: 751: 744: 742: 738: 733: 729: 724: 719: 715: 711: 707: 703: 699: 695: 691: 684: 681: 676: 670: 662: 658: 653: 648: 644: 638: 634: 630: 626: 619: 616: 611: 607: 602: 597: 593: 589: 585: 581: 577: 570: 567: 562: 558: 553: 548: 544: 540: 536: 532: 528: 521: 519: 515: 510: 506: 501: 496: 492: 488: 484: 480: 476: 469: 467: 463: 458: 454: 450: 446: 442: 438: 434: 430: 426: 422: 415: 412: 401: 397: 391: 388: 383: 379: 375: 371: 366: 361: 357: 353: 349: 342: 340: 336: 331: 327: 323: 319: 315: 311: 307: 303: 296: 294: 292: 288: 283: 279: 274: 269: 265: 261: 257: 253: 249: 245: 241: 234: 232: 228: 223: 219: 214: 209: 205: 201: 197: 193: 189: 182: 179: 174: 170: 165: 160: 156: 152: 148: 144: 140: 133: 130: 123: 121: 118: 110: 108: 105: 96: 94: 92: 83: 81: 74: 72: 70: 63:Investigation 62: 60: 54: 52: 49: 45: 40: 36: 28: 26: 23: 22:Richard Hynes 19: 1082:Cell biology 1045: 1041: 1035: 992: 989:Biology Open 988: 932: 928: 918: 909: 868: 864: 857: 814: 810: 800: 760:(354): rs7. 757: 753: 697: 693: 683: 624: 618: 583: 579: 569: 534: 530: 482: 479:EMBO Reports 478: 427:(167): pt2. 424: 420: 414: 403:. 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Index

Richard Hynes
integrins
cadherin
proteomic
mass spectrometry
proximity biotinylation
αv-class integrins
post translational modification
evolved
"The echinoderm adhesome"
doi
10.1016/j.ydbio.2006.07.044
PMC
3565218
PMID
16950242
"Functional atlas of the integrin adhesome"
doi
10.1038/ncb0807-858
PMC
2735470
PMID
17671451


"The switchable integrin adhesome"
doi
10.1242/jcs.066183
ISSN
0021-9533

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