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Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly.

Horton ER, Byron A, Askari JA, Ng DH, Millon-Frémillon A, Robertson J, Koper EJ, Paul NR, Warwood S, Knight D, Humphries JD, Humphries MJ - Nat. Cell Biol. (2015)

Bottom Line: Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome.Analysis of this data set reveals the functional diversity of proteins in IACs and establishes a consensus adhesome of 60 proteins.The definition of this consensus view of integrin adhesome components provides a resource for the research community.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.

ABSTRACT
Integrin receptor activation initiates the formation of integrin adhesion complexes (IACs) at the cell membrane that transduce adhesion-dependent signals to control a multitude of cellular functions. Proteomic analyses of isolated IACs have revealed an unanticipated molecular complexity; however, a global view of the consensus composition and dynamics of IACs is lacking. Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome. Analysis of this data set reveals the functional diversity of proteins in IACs and establishes a consensus adhesome of 60 proteins. The consensus adhesome is likely to represent a core cell adhesion machinery, centred around four axes comprising ILK-PINCH-kindlin, FAK-paxillin, talin-vinculin and α-actinin-zyxin-VASP, and includes underappreciated IAC components such as Rsu-1 and caldesmon. Proteomic quantification of IAC assembly and disassembly detailed the compositional dynamics of the core cell adhesion machinery. The definition of this consensus view of integrin adhesome components provides a resource for the research community.

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Meta-adhesome coverage of the literature-curated adhesome. (a) The proportion of the literature-curated adhesome4 identified in the meta-adhesome is plotted as a percentage bar chart. Proportions of the total literature-curated adhesome (black), intrinsic adhesome components (blue) and associated adhesome components (red) are shown. Numbers of identified proteins are indicated. (b) Line graph showing the cumulative number of literature-curated adhesome proteins identified in at least x proteomic datasets, where x is the minimum (min.) dataset occurrence category. Data for intrinsic (blue) and associated (red) adhesome components are shown. (c) Protein-protein interaction network of the literature-curated adhesome proteins identified in the meta-adhesome. Node size and colour are proportional to the number of proteomic datasets in which a protein was identified; ND, not detected (grey node). Nodes are clustered according to literature-curated adhesome functions; numbers (meta-adhesome/literature-curated adhesome total) and proportions of each functional category identified in the meta-adhesome are indicated in parentheses. Nodes are labelled with gene names for clarity (see Supplementary Table 3 for details).
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Figure 2: Meta-adhesome coverage of the literature-curated adhesome. (a) The proportion of the literature-curated adhesome4 identified in the meta-adhesome is plotted as a percentage bar chart. Proportions of the total literature-curated adhesome (black), intrinsic adhesome components (blue) and associated adhesome components (red) are shown. Numbers of identified proteins are indicated. (b) Line graph showing the cumulative number of literature-curated adhesome proteins identified in at least x proteomic datasets, where x is the minimum (min.) dataset occurrence category. Data for intrinsic (blue) and associated (red) adhesome components are shown. (c) Protein-protein interaction network of the literature-curated adhesome proteins identified in the meta-adhesome. Node size and colour are proportional to the number of proteomic datasets in which a protein was identified; ND, not detected (grey node). Nodes are clustered according to literature-curated adhesome functions; numbers (meta-adhesome/literature-curated adhesome total) and proportions of each functional category identified in the meta-adhesome are indicated in parentheses. Nodes are labelled with gene names for clarity (see Supplementary Table 3 for details).

Mentions: To visualise proteins identified in the meta-adhesome in the context of the literature-curated adhesome4, meta-adhesome proteins were mapped onto adhesome functional categories. In total, 114 (49%) adhesome components were detected across all datasets (Fig. 2a), with almost half (56) detected in three or more datasets (Fig. 2b). The functional categories with the highest coverage in the meta-adhesome were adaptors (46; 65%), actin regulators (14; 82%) and chaperones (3; 100%) (Fig. 2c). GTPases, phosphatases, kinases, channels and adhesion receptors were less well represented. Notably, the receptors most robustly detected were the prominent FN-binding α5β1 and αVβ3 integrins, which confirms the specificity of FN-induced IACs incorporated in the meta-adhesome. The 114 FN-specific adhesome components comprised 87 “intrinsic” and 27 “associated” proteins (Fig. 2a). These data likely reflect the ability of IAC isolation methods to stabilise and identify structural adhesome molecules, such as adaptors and actin regulators. Associated proteins were generally enriched in fewer datasets compared with intrinsic proteins (Fig. 2b), which may be due to the low stoichiometry, context-specificity or highly dynamic and labile nature of associated proteins, such as adhesion-related enzymes, within IACs.


Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly.

Horton ER, Byron A, Askari JA, Ng DH, Millon-Frémillon A, Robertson J, Koper EJ, Paul NR, Warwood S, Knight D, Humphries JD, Humphries MJ - Nat. Cell Biol. (2015)

Meta-adhesome coverage of the literature-curated adhesome. (a) The proportion of the literature-curated adhesome4 identified in the meta-adhesome is plotted as a percentage bar chart. Proportions of the total literature-curated adhesome (black), intrinsic adhesome components (blue) and associated adhesome components (red) are shown. Numbers of identified proteins are indicated. (b) Line graph showing the cumulative number of literature-curated adhesome proteins identified in at least x proteomic datasets, where x is the minimum (min.) dataset occurrence category. Data for intrinsic (blue) and associated (red) adhesome components are shown. (c) Protein-protein interaction network of the literature-curated adhesome proteins identified in the meta-adhesome. Node size and colour are proportional to the number of proteomic datasets in which a protein was identified; ND, not detected (grey node). Nodes are clustered according to literature-curated adhesome functions; numbers (meta-adhesome/literature-curated adhesome total) and proportions of each functional category identified in the meta-adhesome are indicated in parentheses. Nodes are labelled with gene names for clarity (see Supplementary Table 3 for details).
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Related In: Results  -  Collection

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Figure 2: Meta-adhesome coverage of the literature-curated adhesome. (a) The proportion of the literature-curated adhesome4 identified in the meta-adhesome is plotted as a percentage bar chart. Proportions of the total literature-curated adhesome (black), intrinsic adhesome components (blue) and associated adhesome components (red) are shown. Numbers of identified proteins are indicated. (b) Line graph showing the cumulative number of literature-curated adhesome proteins identified in at least x proteomic datasets, where x is the minimum (min.) dataset occurrence category. Data for intrinsic (blue) and associated (red) adhesome components are shown. (c) Protein-protein interaction network of the literature-curated adhesome proteins identified in the meta-adhesome. Node size and colour are proportional to the number of proteomic datasets in which a protein was identified; ND, not detected (grey node). Nodes are clustered according to literature-curated adhesome functions; numbers (meta-adhesome/literature-curated adhesome total) and proportions of each functional category identified in the meta-adhesome are indicated in parentheses. Nodes are labelled with gene names for clarity (see Supplementary Table 3 for details).
Mentions: To visualise proteins identified in the meta-adhesome in the context of the literature-curated adhesome4, meta-adhesome proteins were mapped onto adhesome functional categories. In total, 114 (49%) adhesome components were detected across all datasets (Fig. 2a), with almost half (56) detected in three or more datasets (Fig. 2b). The functional categories with the highest coverage in the meta-adhesome were adaptors (46; 65%), actin regulators (14; 82%) and chaperones (3; 100%) (Fig. 2c). GTPases, phosphatases, kinases, channels and adhesion receptors were less well represented. Notably, the receptors most robustly detected were the prominent FN-binding α5β1 and αVβ3 integrins, which confirms the specificity of FN-induced IACs incorporated in the meta-adhesome. The 114 FN-specific adhesome components comprised 87 “intrinsic” and 27 “associated” proteins (Fig. 2a). These data likely reflect the ability of IAC isolation methods to stabilise and identify structural adhesome molecules, such as adaptors and actin regulators. Associated proteins were generally enriched in fewer datasets compared with intrinsic proteins (Fig. 2b), which may be due to the low stoichiometry, context-specificity or highly dynamic and labile nature of associated proteins, such as adhesion-related enzymes, within IACs.

Bottom Line: Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome.Analysis of this data set reveals the functional diversity of proteins in IACs and establishes a consensus adhesome of 60 proteins.The definition of this consensus view of integrin adhesome components provides a resource for the research community.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.

ABSTRACT
Integrin receptor activation initiates the formation of integrin adhesion complexes (IACs) at the cell membrane that transduce adhesion-dependent signals to control a multitude of cellular functions. Proteomic analyses of isolated IACs have revealed an unanticipated molecular complexity; however, a global view of the consensus composition and dynamics of IACs is lacking. Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome. Analysis of this data set reveals the functional diversity of proteins in IACs and establishes a consensus adhesome of 60 proteins. The consensus adhesome is likely to represent a core cell adhesion machinery, centred around four axes comprising ILK-PINCH-kindlin, FAK-paxillin, talin-vinculin and α-actinin-zyxin-VASP, and includes underappreciated IAC components such as Rsu-1 and caldesmon. Proteomic quantification of IAC assembly and disassembly detailed the compositional dynamics of the core cell adhesion machinery. The definition of this consensus view of integrin adhesome components provides a resource for the research community.

Show MeSH
Related in: MedlinePlus