The integrin adhesome network at a glance

ABSTRACT The adhesion nexus is the site at which integrin receptors bridge intracellular cytoskeletal and extracellular matrix networks. The connection between integrins and the cytoskeleton is mediated by a dynamic integrin adhesion complex (IAC), the components of which transduce chemical and mechanical signals to control a multitude of cellular functions. In this Cell Science at a Glance article and the accompanying poster, we integrate the consensus adhesome, a set of 60 proteins that have been most commonly identified in isolated IAC proteomes, with the literature-curated adhesome, a theoretical network that has been assembled through scholarly analysis of proteins that localise to IACs. The resulting IAC network, which comprises four broad signalling and actin-bridging axes, provides a platform for future studies of the regulation and function of the adhesion nexus in health and disease. Summary: We have generated a new depiction of the integrin adhesome network that integrates experimentally derived IAC proteomes with the literature-curated adhesome to bridge the knowledge gap between these two resources.

[1]  Johannes Köster,et al.  Efficiently mining protein interaction dependencies from large text corpora. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[2]  Bridget E. Begg,et al.  A Proteome-Scale Map of the Human Interactome Network , 2014, Cell.

[3]  M. Humphries,et al.  Microtubule-Dependent Modulation of Adhesion Complex Composition , 2014, PloS one.

[4]  J. Qin,et al.  Kindlin-2 directly binds actin and regulates integrin outside-in signaling , 2016, The Journal of cell biology.

[5]  H. Schiller,et al.  Quantitative proteomics of the integrin adhesome show a myosin II‐dependent recruitment of LIM domain proteins , 2011, EMBO reports.

[6]  R. Fässler,et al.  Mechanosensitivity and compositional dynamics of cell–matrix adhesions , 2013, EMBO reports.

[7]  Julian N. Selley,et al.  Defining the phospho-adhesome through the phosphoproteomic analysis of integrin signalling , 2015, Nature Communications.

[8]  M. Xie,et al.  Microtubules regulate focal adhesion dynamics through MAP4K4. , 2014, Developmental cell.

[9]  Jianmin Wu,et al.  Integrated network analysis platform for protein-protein interactions , 2009, Nature Methods.

[10]  Benjamin Geiger,et al.  The switchable integrin adhesome , 2010, Journal of Cell Science.

[11]  Brian Burke,et al.  A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells , 2012, The Journal of cell biology.

[12]  John R. Yates,et al.  Analysis of the myosinII-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation , 2011, Nature Cell Biology.

[13]  David A Calderwood,et al.  Regulation of integrin-mediated adhesions. , 2015, Current opinion in cell biology.

[14]  David A. Calderwood,et al.  Integrin Cytoplasmic Tail Interactions , 2014, Biochemistry.

[15]  E. Zamir,et al.  Components of cell-matrix adhesions. , 2001, Journal of cell science.

[16]  E. Manser,et al.  Proximity biotinylation provides insight into the molecular composition of focal adhesions at the nanometer scale , 2016, Science Signaling.

[17]  Sylvie Ricard-Blum,et al.  MatrixDB, a database focused on extracellular protein–protein and protein–carbohydrate interactions , 2009, Bioinform..

[18]  B. Geiger,et al.  Dynamic regulation of the structure and functions of integrin adhesions. , 2013, Developmental cell.

[19]  D. Cole,et al.  Bone fragility, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features: a newly recognized type of osteogenesis imperfecta. , 1987, The Journal of pediatrics.

[20]  M. Mann,et al.  β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments , 2013, Nature Cell Biology.

[21]  Adam Byron,et al.  Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly , 2015, Nature Cell Biology.

[22]  J. Heino,et al.  Tumor promoter PMA enhances kindlin-2 and decreases vimentin recruitment into cell adhesion sites. , 2016, The international journal of biochemistry & cell biology.

[23]  Adam Byron,et al.  Proteomic Analysis of Integrin-Associated Complexes Identifies RCC2 as a Dual Regulator of Rac1 and Arf6 , 2009, Science Signaling.

[24]  Zhenhuan Guo,et al.  E-cadherin interactome complexity and robustness resolved by quantitative proteomics , 2014, Science Signaling.

[25]  Tamar Geiger,et al.  Opening the floodgates: proteomics and the integrin adhesome. , 2012, Current opinion in cell biology.

[26]  F. Glorieux,et al.  Cole-Carpenter syndrome is caused by a heterozygous missense mutation in P4HB. , 2015, American journal of human genetics.

[27]  Benjamin Geiger,et al.  Molecular architecture and function of matrix adhesions. , 2011, Cold Spring Harbor perspectives in biology.

[28]  Mark R Morgan,et al.  Emerging properties of adhesion complexes: what are they and what do they do? , 2015, Trends in cell biology.

[29]  J. Yates,et al.  Isolation of focal adhesion proteins for biochemical and proteomic analysis. , 2012, Methods in molecular biology.

[30]  B. Geiger,et al.  The integrin adhesome: from genes and proteins to human disease , 2014, Nature Reviews Molecular Cell Biology.

[31]  S. Itzkovitz,et al.  Functional atlas of the integrin adhesome , 2007, Nature Cell Biology.

[32]  M. Humphries,et al.  Isolation of Integrin‐Based Adhesion Complexes , 2015, Current protocols in cell biology.

[33]  Z. Kam,et al.  Differential Effect of Actomyosin Relaxation on the Dynamic Properties of Focal Adhesion Proteins , 2013, PloS one.

[34]  M. Humphries,et al.  Proteomic analysis of α4β1 integrin adhesion complexes reveals α-subunit-dependent protein recruitment , 2012, Proteomics.

[35]  Katja Ickstadt,et al.  Symmetric exchange of multi-protein building blocks between stationary focal adhesions and the cytosol , 2014, eLife.

[36]  Trushar R. Patel,et al.  LAR protein tyrosine phosphatase regulates focal adhesions through CDK1 , 2016, Journal of Cell Science.

[37]  J. Lippincott-Schwartz,et al.  Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure , 2009, Proceedings of the National Academy of Sciences.

[38]  E. Zamir,et al.  Molecular complexity and dynamics of cell-matrix adhesions. , 2001, Journal of cell science.

[39]  M. Frame,et al.  Adhesion protein networks reveal functions proximal and distal to cell-matrix contacts , 2016, Current opinion in cell biology.

[40]  A. Lambacher,et al.  Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin , 2016, eLife.

[41]  M. Humphries,et al.  Mechanosensitivity of integrin adhesion complexes: role of the consensus adhesome. , 2016, Experimental cell research.

[42]  Michael W. Davidson,et al.  Nanoscale architecture of integrin-based cell adhesions , 2010, Nature.

[43]  M. Humphries,et al.  Proteomic analysis of integrin‐associated complexes from mesenchymal stem cells , 2015, Proteomics. Clinical applications.

[44]  S. Barry,et al.  Modulation of FAK and Src adhesion signaling occurs independently of adhesion complex composition , 2016, The Journal of cell biology.

[45]  Donald E Ingber,et al.  Investigating complexity of protein-protein interactions in focal adhesions. , 2008, Biochemical and biophysical research communications.

[46]  J. Pouwels,et al.  Integrin inactivators: balancing cellular functions in vitro and in vivo , 2013, Nature Reviews Molecular Cell Biology.

[47]  Daniel Choquet,et al.  Integrins β1 and β3 exhibit distinct dynamic nanoscale organizations inside focal adhesions , 2012, Nature Cell Biology.

[48]  K. Lilley,et al.  Protein Neighbors and Proximity Proteomics* , 2015, Molecular & Cellular Proteomics.

[49]  B. Goud,et al.  Integrin endosomal signalling suppresses anoikis , 2015, Nature Cell Biology.

[50]  K. Khoo,et al.  GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment , 2014, Journal of Cell Science.

[51]  Alexandra M. Greiner,et al.  Vinculin Regulates the Recruitment and Release of Core Focal Adhesion Proteins in a Force-Dependent Manner , 2013, Current Biology.

[52]  Colin K. Choi,et al.  A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting , 2015, Nature Communications.