Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1106K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rezniczek, G. A. Articles by Wiche, G. Search for Related Content PubMed PubMed Citation Articles by Rezniczek, G. A. Articles by Wiche, G. Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/1998//209 $5.00
The Journal of Cell Biology, Volume 141, Number 1, , 1998 209-225

Linking Integrin ₆β₄-based Cell Adhesion to the Intermediate Filament Cytoskeleton: Direct Interaction between the β₄ Subunit and Plectin at Multiple Molecular Sites

Institute of Biochemistry and Molecular Cell Biology, Vienna Biocenter, 1030 Vienna, Austria

Recent studies with patients suffering from epidermolysis bullosa simplex associated with muscular dystrophy and the targeted gene disruption in mice suggested that plectin, a versatile cytoskeletal linker and intermediate filament-binding protein, may play an essential role in hemidesmosome integrity and stabilization. To define plectin's interactions with hemidesmosomal proteins on the molecular level, we studied its interaction with the uniquely long cytoplasmic tail domain of the β₄ subunit of the basement membrane laminin receptor integrin ₆β₄ that has been implicated in connecting the transmembrane integrin complex with hemidesmosome-anchored cytokeratin filaments. In vitro binding and in vivo cotransfection assays, using recombinant mutant forms of both proteins, revealed their direct interaction via multiple molecular domains. Furthermore, we show in vitro self-interaction of integrin β₄ cytoplasmic domains, as well as disruption of intermediate filament network arrays and dislocation of hemidesmosome-associated endogenous plectin upon ectopic overexpression of this domain in PtK2 and/or 804G cells. The close association of plectin molecules with hemidesmosomal structures and their apparent random orientation was indicated by gold immunoelectron microscopy using domain-specific antibodies. Our data support a model in which plectin stabilizes hemidesmosomes, via directly interlinking integrin β₄ subunits and cytokeratin filaments.

Abbreviations used in this paper: EBS-MD, epidermolysis bullosa simplex combined with muscular dystrophy; FNIII, fibronectin type III repeat; GFP, green fluorescent protein; IF, intermediate filament.

Address all correspondence to Gerhard Wiche, Vienna Biocenter, Institute of Biochemistry and Molecular Cell Biology, University of Vienna, Dr. Bohr-Gasse 9, 1030 Vienna, Austria. Tel.: 43 (1) 79515-5119. Fax: 43 (1) 79515-5121. E-mail: wiche{at}abc.univie.ac.at

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Kostan, J., Gregor, M., Walko, G., Wiche, G. (2009). Plectin Isoform-dependent Regulation of Keratin-Integrin {alpha}6{beta}4 Anchorage via Ca2+/Calmodulin. J. Biol. Chem. 284: 18525-18536 [Abstract] [Full Text]  
• Na, S., Chowdhury, F., Tay, B., Ouyang, M., Gregor, M., Wang, Y., Wiche, G., Wang, N. (2009). Plectin contributes to mechanical properties of living cells. Am. J. Physiol. Cell Physiol. 296: C868-C877 [Abstract] [Full Text]  
• Hijikata, T., Nakamura, A., Isokawa, K., Imamura, M., Yuasa, K., Ishikawa, R., Kohama, K., Takeda, S., Yorifuji, H. (2008). Plectin 1 links intermediate filaments to costameric sarcolemma through {beta}-synemin, {alpha}-dystrobrevin and actin. J. Cell Sci. 121: 2062-2074 [Abstract] [Full Text]  
• Mruk, D. D., Silvestrini, B., Cheng, C. Y. (2008). Anchoring Junctions As Drug Targets: Role in Contraceptive Development. Pharmacol. Rev. 60: 146-180 [Abstract] [Full Text]  
• Wilhelmsen, K., Litjens, S. H.M., Kuikman, I., Margadant, C., van Rheenen, J., Sonnenberg, A. (2007). Serine Phosphorylation of the Integrin beta4 Subunit Is Necessary for Epidermal Growth Factor Receptor induced Hemidesmosome Disruption. Mol. Biol. Cell 18: 3512-3522 [Abstract] [Full Text]  
• Ackerl, R., Walko, G., Fuchs, P., Fischer, I., Schmuth, M., Wiche, G. (2007). Conditional targeting of plectin in prenatal and adult mouse stratified epithelia causes keratinocyte fragility and lesional epidermal barrier defects. J. Cell Sci. 120: 2435-2443 [Abstract] [Full Text]  
• Rezniczek, G. A., Konieczny, P., Nikolic, B., Reipert, S., Schneller, D., Abrahamsberg, C., Davies, K. E., Winder, S. J., Wiche, G. (2007). Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with {beta}-dystroglycan. JCB 176: 965-977 [Abstract] [Full Text]  
• Sehgal, B. U., DeBiase, P. J., Matzno, S., Chew, T.-L., Claiborne, J. N., Hopkinson, S. B., Russell, A., Marinkovich, M. P., Jones, J. C. R. (2006). Integrin beta4 Regulates Migratory Behavior of Keratinocytes by Determining Laminin-332 Organization. J. Biol. Chem. 281: 35487-35498 [Abstract] [Full Text]  
• Osmanagic-Myers, S., Gregor, M., Walko, G., Burgstaller, G., Reipert, S., Wiche, G. (2006). Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in cellular stress response and migration. JCB 174: 557-568 [Abstract] [Full Text]  
• Wilhelmsen, K., Litjens, S. H.M., Sonnenberg, A. (2006). Multiple Functions of the Integrin {alpha}6{beta}4 in Epidermal Homeostasis and Tumorigenesis. Mol. Cell. Biol. 26: 2877-2886 [Full Text]  
• Raymond, K., Kreft, M., Janssen, H., Calafat, J., Sonnenberg, A. (2005). Keratinocytes display normal proliferation, survival and differentiation in conditional {beta}4-integrin knockout mice. J. Cell Sci. 118: 1045-1060 [Abstract] [Full Text]  
• Rabinovitz, I., Tsomo, L., Mercurio, A. M. (2004). Protein Kinase C-{alpha} Phosphorylation of Specific Serines in the Connecting Segment of the {beta}4 Integrin Regulates the Dynamics of Type II Hemidesmosomes. Mol. Cell. Biol. 24: 4351-4360 [Abstract] [Full Text]  
• Breitkreutz, D., Mirancea, N., Schmidt, C., Beck, R., Werner, U., Stark, H.-J., Gerl, M., Fusenig, N. E. (2004). Inhibition of basement membrane formation by a nidogen-binding laminin {gamma}1-chain fragment in human skin-organotypic cocultures. J. Cell Sci. 117: 2611-2622 [Abstract] [Full Text]  
• Koster, J., van Wilpe, S., Kuikman, I., Litjens, S.H.M., Sonnenberg, A. (2004). Role of Binding of Plectin to the Integrin {beta}4 Subunit in the Assembly of Hemidesmosomes. Mol. Biol. Cell 15: 1211-1223 [Abstract] [Full Text]  
• Rezniczek, G. A., Abrahamsberg, C., Fuchs, P., Spazierer, D., Wiche, G. (2003). Plectin 5'-transcript diversity: short alternative sequences determine stability of gene products, initiation of translation and subcellular localization of isoforms. Hum Mol Genet 12: 3181-3194 [Abstract] [Full Text]  
• Litjens, S. H.M., Koster, J., Kuikman, I., van Wilpe, S., de Pereda, J. M., Sonnenberg, A. (2003). Specificity of Binding of the Plectin Actin-binding Domain to {beta}4 Integrin. Mol. Biol. Cell 14: 4039-4050 [Abstract] [Full Text]  
• Roper, K., Brown, N. H. (2003). Maintaining epithelial integrity: a function for gigantic spectraplakin isoforms in adherens junctions. JCB 162: 1305-1315 [Abstract] [Full Text]  
• Koster, J., Geerts, D., Favre, B., Borradori, L., Sonnenberg, A. (2003). Analysis of the interactions between BP180, BP230, plectin and the integrin {alpha}6{beta}4 important for hemidesmosome assembly. J. Cell Sci. 116: 387-399 [Abstract] [Full Text]  
• Roper, K., Gregory, S. L., Brown, N. H. (2002). The `Spectraplakins': cytoskeletal giants with characteristics of both spectrin and plakin families. J. Cell Sci. 115: 4215-4225 [Abstract] [Full Text]  
• Suzuki, T., Nakamoto, T., Ogawa, S., Seo, S., Matsumura, T., Tachibana, K., Morimoto, C., Hirai, H. (2002). MICAL, a Novel CasL Interacting Molecule, Associates with Vimentin. J. Biol. Chem. 277: 14933-14941 [Abstract] [Full Text]  
• Beil, M., Leser, J., Lutz, M. P., Gukovskaya, A., Seufferlein, T., Lynch, G., Pandol, S. J., Adler, G. (2002). Caspase 8-mediated cleavage of plectin precedes F-actin breakdown in acinar cells during pancreatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 282: G450-G460 [Abstract] [Full Text]  
• Mariotti, A., Kedeshian, P. A., Dans, M., Curatola, A. M., Gagnoux-Palacios, L., Giancotti, F. G. (2001). EGF-R signaling through Fyn kinase disrupts the function of integrin {alpha}6{beta}4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion. JCB 155: 447-458 [Abstract] [Full Text]  
• Shaw, L. M. (2001). Identification of Insulin Receptor Substrate 1 (IRS-1) and IRS-2 as Signaling Intermediates in the {alpha}6{beta}4 Integrin-Dependent Activation of Phosphoinositide 3-OH Kinase and Promotion of Invasion. Mol. Cell. Biol. 21: 5082-5093 [Abstract] [Full Text]  
• Brown, M. J., Hallam, J. A., Liu, Y., Yamada, K. M., Shaw, S. (2001). Cutting Edge: Integration of Human T Lymphocyte Cytoskeleton by the Cytolinker Plectin. J. Immunol. 167: 641-645 [Abstract] [Full Text]  
• Kumari, S., Bhol, K. C., Simmons, R. K., Razzaque, M. S., Letko, E., Foster, C. S., Ahmed, A. R. (2001). Identification of Ocular Cicatricial Pemphigoid Antibody Binding Site(s) in Human {beta}4 Integrin. IOVS 42: 379-385 [Abstract] [Full Text]  
• Bauer, J. W., Rouan, F., Kofler, B., Rezniczek, G. A., Kornacker, I., Muss, W., Hametner, R., Klausegger, A., Huber, A., Pohla-Gubo, G., Wiche, G., Uitto, J., Hintner, H. (2001). A Compound Heterozygous One Amino-Acid Insertion/Nonsense Mutation in the Plectin Gene Causes Epidermolysis Bullosa Simplex with Plectin Deficiency. Am. J. Pathol. 158: 617-625 [Abstract] [Full Text]  
• Gonzalez, A. M., Otey, C., Edlund, M., Jones, J. C. R. (2001). Interactions of a hemidesmosome component and actinin family members. J. Cell Sci. 114: 4197-4206 [Abstract] [Full Text]  
• Fontao, L., Geerts, D., Kuikman, I., Koster, J., Kramer, D., Sonnenberg, A. (2001). The interaction of plectin with actin: evidence for cross-linking of actin filaments by dimerization of the actin-binding domain of plectin. J. Cell Sci. 114: 2065-2076 [Abstract] [Full Text]  
• Fuchs, E., Karakesisoglou, I. (2001). Bridging cytoskeletal intersections. Genes Dev. 15: 1-14 [Full Text]  
• Sun, D, Leung, C., Liem, R. (2001). Characterization of the microtubule binding domain of microtubule actin crosslinking factor (MACF): identification of a novel group of microtubule associated proteins. J. Cell Sci. 114: 161-172 [Abstract]  
• Sterk, L. M.Th., Geuijen, C. A.W., Oomen, L. C.J.M., Calafat, J., Janssen, H., Sonnenberg, A. (2000). The Tetraspan Molecule Cd151, a Novel Constituent of Hemidesmosomes, Associates with the Integrin {alpha}6{beta}4 and May Regulate the Spatial Organization of Hemidesmosomes. JCB 149: 969-982 [Abstract] [Full Text]  
• Karakesisoglou, I., Yang, Y., Fuchs, E. (2000). An Epidermal Plakin That Integrates Actin and Microtubule Networks at Cellular Junctions. JCB 149: 195-208 [Abstract] [Full Text]  
• Nievers, M., Kuikman, I, Geerts, D, Leigh, I., Sonnenberg, A (2000). Formation of hemidesmosome-like structures in the absence of ligand binding by the (alpha)6(beta)4 integrin requires binding of HD1/plectin to the cytoplasmic domain of the (beta)4 integrin subunit. J. Cell Sci. 113: 963-973 [Abstract]  
• Hopkinson, S. B., Jones, J. C. R. (2000). The N Terminus of the Transmembrane Protein BP180 Interacts with the N-terminal Domain of BP230, Thereby Mediating Keratin Cytoskeleton Anchorage to the Cell Surface at the Site of the Hemidesmosome. Mol. Biol. Cell 11: 277-286 [Abstract] [Full Text]  
• Leung, C. L., Sun, D., Zheng, M., Knowles, D. R., Liem, R. K.H. (1999). Microtubule Actin Cross-Linking Factor (Macf): A Hybrid of Dystonin and Dystrophin That Can Interact with the Actin and Microtubule Cytoskeletons. JCB 147: 1275-1286 [Abstract] [Full Text]  
• Steinert, P. M., Marekov, L. N. (1999). Initiation of Assembly of the Cell Envelope Barrier Structure of Stratified Squamous Epithelia. Mol. Biol. Cell 10: 4247-4261 [Abstract] [Full Text]  
• Geerts, D., Fontao, L., Nievers, M. G., Schaapveld, R. Q.J., Purkis, P. E., Wheeler, G. N., Lane, E. B., Leigh, I. M., Sonnenberg, A. (1999). Binding of Integrin {alpha}6{beta}4 to Plectin Prevents Plectin Association with F-Actin but Does Not Interfere with Intermediate Filament Binding. JCB 147: 417-434 [Abstract] [Full Text]  
• Basora, N., Herring-Gillam, F. E., Boudreau, F., Perreault, N., Pageot, L.-P., Simoneau, M., Bouatrouss, Y., Beaulieu, J.-F. (1999). Expression of Functionally Distinct Variants of the beta 4A Integrin Subunit in Relation to the Differentiation State in Human Intestinal Cells. J. Biol. Chem. 274: 29819-29825 [Abstract] [Full Text]  
• Rabinovitz, I., Toker, A., Mercurio, A. M. (1999). Protein Kinase C-Dependent Mobilization of the {alpha}6{beta}4 Integrin from Hemidesmosomes and Its Association with Actin-Rich Cell Protrusions Drive the Chemotactic Migration of Carcinoma Cells. JCB 146: 1147-1160 [Abstract] [Full Text]  
• Sanvito, F., Piatti, S., Villa, A., Bossi, M., Lucchini, G., Marchisio, P. C., Biffo, S. (1999). The {beta}4 Integrin Interactor p27BBP/eIF6 Is an Essential Nuclear Matrix Protein Involved in 60S Ribosomal Subunit Assembly. JCB 144: 823-838 [Abstract] [Full Text]  
• North, A., Bardsley, W., Hyam, J, Bornslaeger, E., Cordingley, H., Trinnaman, B, Hatzfeld, M, Green, K., Magee, A., Garrod, D. (1999). Molecular map of the desmosomal plaque. J. Cell Sci. 112: 4325-4336 [Abstract]  
• Hijikata, T, Murakami, T, Imamura, M, Fujimaki, N, Ishikawa, H (1999). Plectin is a linker of intermediate filaments to Z-discs in skeletal muscle fibers. J. Cell Sci. 112: 867-876 [Abstract]  
• O'Connor, K. L., Shaw, L. M., Mercurio, A. M. (1998). Release of cAMP Gating by the {alpha}6{beta}4 Integrin Stimulates Lamellae Formation and the Chemotactic Migration of Invasive Carcinoma Cells. JCB 143: 1749-1760 [Abstract] [Full Text]  
• Andrä, K., Nikolic, B., Stöcher, M., Drenckhahn, D., Wiche, G. (1998). Not just scaffolding: plectin regulates actin dynamics in cultured cells. Genes Dev. 12: 3442-3451 [Abstract] [Full Text]  
• Wiche, G (1998). Role of plectin in cytoskeleton organization and dynamics. J. Cell Sci. 111: 2477-2486 [Abstract]  
• Homan, S., Mercurio, A., LaFlamme, S. (1998). Endothelial cells assemble two distinct alpha6beta4-containing vimentin-associated structures: roles for ligand binding and the beta4 cytoplasmic tail. J. Cell Sci. 111: 2717-2728 [Abstract]  
• Favre, B., Fontao, L., Koster, J., Shafaatian, R., Jaunin, F., Saurat, J.-H., Sonnenberg, A., Borradori, L. (2001). The Hemidesmosomal Protein Bullous Pemphigoid Antigen 1 and the Integrin beta 4 Subunit Bind to ERBIN. MOLECULAR CLONING OF MULTIPLE ALTERNATIVE SPLICE VARIANTS OF ERBIN AND ANALYSIS OF THEIR TISSUE EXPRESSION. J. Biol. Chem. 276: 32427-32436 [Abstract] [Full Text]  
• Dellambra, E., Prislei, S., Salvati, A. L., Madeddu, M. L., Golisano, O., Siviero, E., Bondanza, S., Cicuzza, S., Orecchia, A., Giancotti, F. G., Zambruno, G., De Luca, M. (2001). Gene Correction of Integrin beta 4-dependent Pyloric Atresia-Junctional Epidermolysis Bullosa Keratinocytes Establishes a Role for beta 4 Tyrosines 1422 and 1440 in Hemidesmosome Assembly. J. Biol. Chem. 276: 41336-41342 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents