Emerging properties of adhesion complexes: what are they and what do they do?

The regulation of cell adhesion machinery is central to a wide variety of developmental and pathological processes and occurs primarily within integrin-associated adhesion complexes. Here, we review recent advances that have furthered our understanding of the composition, organisation, and dynamics of these complexes, and provide an updated view on their emerging functions. Key findings are that adhesion complexes contain both core and non-canonical components. As a result of the dramatic increase in the range of components observed in adhesion complexes by proteomics, we comment on newly emerging functions for adhesion signalling. We conclude that, from a cellular or tissue systems perspective, adhesion signalling should be viewed as an emergent property of both the core and non-canonical adhesion complex components.

[1]  Michael P. Sheetz,et al.  Stretching Single Talin Rod Molecules Activates Vinculin Binding , 2009, Science.

[2]  Nicola Elvassore,et al.  Role of YAP/TAZ in mechanotransduction , 2011, Nature.

[3]  P. Janmey,et al.  Augmentation of integrin-mediated mechanotransduction by hyaluronic acid. , 2014, Biomaterials.

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

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

[6]  Richard G. W. Anderson,et al.  Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization , 2005, Nature Cell Biology.

[7]  M. Steinhauser,et al.  Quantitative imaging of subcellular metabolism with stable isotopes and multi-isotope imaging mass spectrometry. , 2013, Seminars in cell & developmental biology.

[8]  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.

[9]  Kazuro Furukawa,et al.  Ganglioside GD3 Enhances Adhesion Signals and Augments Malignant Properties of Melanoma Cells by Recruiting Integrins to Glycolipid-enriched Microdomains* , 2010, The Journal of Biological Chemistry.

[10]  T. Ross,et al.  Integrins in mechanotransduction. , 2013, Current opinion in cell biology.

[11]  Kenneth M. Yamada,et al.  Transmembrane crosstalk between the extracellular matrix and the cytoskeleton , 2001, Nature Reviews Molecular Cell Biology.

[12]  Hisataka Sabe,et al.  Interaction of Paxillin with Poly(A)-Binding Protein 1 and Its Role in Focal Adhesion Turnover and Cell Migration , 2005, Molecular and Cellular Biology.

[13]  M. Davidson,et al.  The cancer glycocalyx mechanically primes integrin-mediated growth and survival , 2014, Nature.

[14]  W. Ens,et al.  Characterization of IQGAP1-containing complexes in NK-like cells: evidence for Rac 2 and RACK1 association during homotypic adhesion. , 2007, Journal of proteome research.

[15]  Robert P. Jenkins,et al.  Mechano-transduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer associated fibroblasts , 2013, Nature Cell Biology.

[16]  Xiaoping Du,et al.  A directional switch of integrin signaling and a new anti-thrombotic strategy , 2013, Nature.

[17]  J. Shabanowitz,et al.  Identification of phosphorylation sites in GIT1. , 2006 .

[18]  Masaaki Yoshigi,et al.  Stretch-induced actin remodeling requires targeting of zyxin to stress fibers and recruitment of actin regulators , 2012, Molecular biology of the cell.

[19]  Daniel St Johnston,et al.  Moving messages: the intracellular localization of mRNAs , 2005, Nature Reviews Molecular Cell Biology.

[20]  K. Burridge,et al.  The on-off relationship of Rho and Rac during integrin-mediated adhesion and cell migration , 2014, Small GTPases.

[21]  K. Nose,et al.  Uni-axial stretching regulates intracellular localization of Hic-5 expressed in smooth-muscle cells in vivo , 2005, Journal of Cell Science.

[22]  A. Paller,et al.  Ganglioside modulates ligand binding to the epidermal growth factor receptor. , 2001, The Journal of investigative dermatology.

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

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

[25]  E. Ruoslahti,et al.  An Arg-Gly-Asp-directed receptor on the surface of human melanoma cells exists in an divalent cation-dependent functional complex with the disialoganglioside GD2 , 1987, The Journal of cell biology.

[26]  N. Pedersen,et al.  Ubiquitination of alpha 5 beta 1 integrin controls fibroblast migration through lysosomal degradation of fibronectin-integrin complexes. , 2010, Developmental cell.

[27]  Brenton D. Hoffman,et al.  Dynamic molecular processes mediate cellular mechanotransduction , 2011, Nature.

[28]  L. Foster,et al.  Mapping the integrin-linked kinase interactome using SILAC. , 2008, Journal of proteome research.

[29]  Christoph Ballestrem,et al.  Vinculin controls focal adhesion formation by direct interactions with talin and actin , 2007, The Journal of cell biology.

[30]  Toshihide Kobayashi,et al.  Gangliosides and β1‐Integrin Are Required for Caveolae and Membrane Domains , 2010, Traffic.

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

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

[33]  G. Gundersen,et al.  Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells , 2009, The Journal of cell biology.

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

[35]  Khuloud Jaqaman,et al.  Regulation from within: the cytoskeleton in transmembrane signaling. , 2012, Trends in cell biology.

[36]  R. Fässler,et al.  Regulation of membrane traffic by integrin signaling. , 2011, Trends in cell biology.

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

[38]  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.

[39]  Y. Takada,et al.  Identification of proteins that associate with integrin α2 by proteomic analysis in human fibrosarcoma HT‐1080 cells , 2012, Journal of cellular physiology.

[40]  S. Morley,et al.  Localization of ribosomes and translation initiation factors to talin/β3‐integrin‐enriched adhesion complexes in spreading and migrating mammalian cells , 2010, Biology of the cell.

[41]  J. Norman,et al.  Rab25 and CLIC3 Collaborate to Promote Integrin Recycling from Late Endosomes/Lysosomes and Drive Cancer Progression , 2012, Developmental cell.

[42]  Andrés J. García,et al.  Cyclic mechanical reinforcement of integrin-ligand interactions. , 2013, Molecular cell.

[43]  A. von Kriegsheim,et al.  RCP-driven α5β1 recycling suppresses Rac and promotes RhoA activity via the RacGAP1–IQGAP1 complex , 2013, The Journal of cell biology.

[44]  J. Shabanowitz,et al.  Methods for the detection of paxillin post-translational modifications and interacting proteins by mass spectrometry. , 2005, Journal of proteome research.

[45]  J. Norman,et al.  Neuropilin-1/GIPC1 Signaling Regulates α5β1 Integrin Traffic and Function in Endothelial Cells , 2009, PLoS biology.

[46]  Yong Ho Bae,et al.  A FAK-Cas-Rac-Lamellipodin Signaling Module Transduces Extracellular Matrix Stiffness into Mechanosensitive Cell Cycling , 2014, Science Signaling.

[47]  G. Mills,et al.  Rab25 associates with α5β1 integrin to promote invasive migration in 3D microenvironments , 2007 .

[48]  P. Defilippi,et al.  Integrin signalling adaptors: not only figurants in the cancer story , 2010, Nature Reviews Cancer.

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

[50]  B. Wehrle-Haller Assembly and disassembly of cell matrix adhesions. , 2012, Current opinion in cell biology.

[51]  H. Dietz,et al.  Integrin Modulating Therapies Prevent Fibrosis and Autoimmunity in Genetic Mouse Models of Scleroderma , 2013, Nature.

[52]  S. Goodman,et al.  Integrins as therapeutic targets. , 2012, Trends in pharmacological sciences.

[53]  O. Kallioniemi,et al.  Integrin trafficking regulated by Rab21 is necessary for cytokinesis. , 2008, Developmental cell.

[54]  M. Morgan,et al.  Fibronectin remodelling: cell-mediated regulation of the microenvironment. , 2015, Biochemical Society transactions.

[55]  S. Bicciato,et al.  The Hippo Transducer TAZ Confers Cancer Stem Cell-Related Traits on Breast Cancer Cells , 2011, Cell.

[56]  I. Campbell,et al.  Talins and kindlins: partners in integrin-mediated adhesion , 2013, Nature Reviews Molecular Cell Biology.

[57]  M. Humphries,et al.  Adhesion signalling complexes , 2010, Current Biology.

[58]  Jie Yan,et al.  Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation , 2014, Scientific Reports.

[59]  M. Davidson,et al.  The Membrane‐Associated Protein, Supervillin, Accelerates F‐Actin‐Dependent Rapid Integrin Recycling and Cell Motility , 2010, Traffic.

[60]  J. Norman,et al.  Integrins: masters and slaves of endocytic transport , 2009, Nature Reviews Molecular Cell Biology.

[61]  D. Scott,et al.  Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts , 2007, Nature Cell Biology.

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

[63]  Amber L. Wells,et al.  β-Actin mRNA compartmentalization enhances focal adhesion stability and directs cell migration. , 2012, Genes & Development.

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

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

[66]  Paul A. Janmey,et al.  Cell-Cycle Control by Physiological Matrix Elasticity and In Vivo Tissue Stiffening , 2009, Current Biology.

[67]  M. Roberts,et al.  Paxillin Associates with Poly(A)-binding Protein 1 at the Dense Endoplasmic Reticulum and the Leading Edge of Migrating Cells* , 2002, The Journal of Biological Chemistry.

[68]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[69]  M. Humphries,et al.  Synergistic control of cell adhesion by integrins and syndecans , 2007, Nature Reviews Molecular Cell Biology.

[70]  R. Fässler,et al.  Sorting nexin 17 prevents lysosomal degradation of β1 integrins by binding to the β1-integrin tail , 2012, Nature Cell Biology.

[71]  Robert G. Parton,et al.  Cells Respond to Mechanical Stress by Rapid Disassembly of Caveolae , 2011, Cell.

[72]  Taekjip Ha,et al.  Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics , 2010, Nature.

[73]  I. Campbell,et al.  Integrin structure, activation, and interactions. , 2011, Cold Spring Harbor perspectives in biology.

[74]  Masaaki Yoshigi,et al.  Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement , 2005, The Journal of cell biology.

[75]  Fiona M. Watt,et al.  Role of the extracellular matrix in regulating stem cell fate , 2013, Nature Reviews Molecular Cell Biology.

[76]  G. Gundersen,et al.  Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase , 2005, Nature Cell Biology.

[77]  Amber L. Couzens,et al.  The CRAPome: a Contaminant Repository for Affinity Purification Mass Spectrometry Data , 2013, Nature Methods.

[78]  H. Stenmark,et al.  The ESCRT machinery mediates polarization of fibroblasts through regulation of myosin light chain , 2012, Journal of Cell Science.

[79]  Donald E. Ingber,et al.  Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions , 1998, Nature.

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

[81]  B. Geiger,et al.  Regulation of focal adhesion formation by a vinculin-Arp2/3 hybrid complex , 2014, Nature Communications.

[82]  M. Mann,et al.  RNA and RNA Binding Proteins Participate in Early Stages of Cell Spreading through Spreading Initiation Centers , 2004, Cell.

[83]  A. R. Horwitz The origins of the molecular era of adhesion research , 2012, Nature Reviews Molecular Cell Biology.

[84]  N. Elvassore,et al.  A Mechanical Checkpoint Controls Multicellular Growth through YAP/TAZ Regulation by Actin-Processing Factors , 2013, Cell.

[85]  M. Beckerle,et al.  LIM proteins in actin cytoskeleton mechanoresponse. , 2014, Trends in cell biology.

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

[87]  M. Roberts,et al.  PDGF-regulated rab4-dependent recycling of αvβ3 integrin from early endosomes is necessary for cell adhesion and spreading , 2001, Current Biology.

[88]  Donald E Ingber,et al.  Mechanobiology and developmental control. , 2013, Annual review of cell and developmental biology.

[89]  Brett L. Kutscher,et al.  A Conformational Switch in Vinculin Drives Formation and Dynamics of a Talin-Vinculin Complex at Focal Adhesions* , 2006, Journal of Biological Chemistry.

[90]  Guanqing Ou,et al.  Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression , 2014, Nature Medicine.

[91]  Fei Liu,et al.  Biomechanical regulation of mesenchymal cell function , 2013, Current opinion in rheumatology.

[92]  P. Cullen,et al.  SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways , 2012, The Journal of cell biology.

[93]  Bernhard Spengler,et al.  Mass spectrometry imaging with high resolution in mass and space , 2013, Histochemistry and Cell Biology.

[94]  J. Yates,et al.  Regulation of cell migration and survival by focal adhesion targeting of Lasp-1 , 2004, The Journal of cell biology.

[95]  J. Condeelis,et al.  Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1 , 2005, Nature.

[96]  P. Janmey,et al.  From tissue mechanics to transcription factors. , 2013, Differentiation; research in biological diversity.

[97]  S. Corbett,et al.  The fate of internalized α5 integrin is regulated by matrix-capable fibronectin. , 2014, The Journal of surgical research.

[98]  S. Mayor,et al.  Molecules, mechanisms, and cellular roles of clathrin-independent endocytosis. , 2010, Current opinion in cell biology.

[99]  A. Ikai,et al.  Requirement of LIM domains for the transient accumulation of paxillin at damaged stress fibres , 2013, Biology Open.

[100]  Cheng Zhu,et al.  JCB_200810002 1275..1284 , 2009 .

[101]  Michael P. Sheetz,et al.  Force Sensing by Mechanical Extension of the Src Family Kinase Substrate p130Cas , 2006, Cell.

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

[103]  Bin Wu,et al.  Single β-Actin mRNA Detection in Neurons Reveals a Mechanism for Regulating Its Translatability , 2014, Science.

[104]  Donald E. Ingber,et al.  Mechanosensitive mechanisms in transcriptional regulation , 2012, Journal of Cell Science.

[105]  Richard G. W. Anderson,et al.  Integrins Regulate Rac Targeting by Internalization of Membrane Domains , 2004, Science.

[106]  N. Sidenius,et al.  The interaction between uPAR and vitronectin triggers ligand‐independent adhesion signalling by integrins , 2014, The EMBO journal.

[107]  J. Shabanowitz,et al.  FAK phosphorylation sites mapped by mass spectrometry , 2005, Journal of Cell Science.

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

[109]  Martin A. Schwartz,et al.  Cell adhesion: integrating cytoskeletal dynamics and cellular tension , 2010, Nature Reviews Molecular Cell Biology.

[110]  D. Griggs,et al.  Selective αv integrin depletion identifies a core, targetable molecular pathway that regulates fibrosis across solid organs , 2013, Nature Network Boston.

[111]  C. Belani,et al.  Volociximab in cancer , 2012, Expert opinion on biological therapy.

[112]  M. Beckerle,et al.  LIM Domains Target Actin Regulators Paxillin and Zyxin to Sites of Stress Fiber Strain , 2013, PloS one.

[113]  Colin K. Choi,et al.  Rac1 is deactivated at integrin activation sites through an IQGAP1–filamin-A–RacGAP1 pathway , 2013, Journal of Cell Science.

[114]  J. Kunz,et al.  Focal adhesion disassembly requires clathrin‐dependent endocytosis of integrins , 2009, FEBS letters.

[115]  M. Humphries,et al.  Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling , 2013, Developmental cell.

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

[117]  J. Ivaska,et al.  Distinct Recycling of Active and Inactive β1 Integrins , 2012, Traffic.

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

[119]  H. Kessler,et al.  Integrin modulators: a patent review , 2013, Expert opinion on therapeutic patents.

[120]  Jonathan A. Cooper,et al.  Quantitative proteomics identifies a Dab2/integrin module regulating cell migration , 2009, The Journal of cell biology.

[121]  S. Chien,et al.  Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity , 2011, Proceedings of the National Academy of Sciences.

[122]  Paul Martin,et al.  A Syndecan-4 Hair Trigger Initiates Wound Healing through Caveolin- and RhoG-Regulated Integrin Endocytosis , 2011, Developmental cell.