Role of Binding of Plectin to the Integrin β4 Subunit in the Assembly of Hemidesmosomes

Koster, Jan; Wilpe, Sandra van; Kuikman, Ingrid; Litjens, Sandy H.M.; Sonnenberg, Arnoud

doi:10.1091/mbc.e03-09-0697

Cited by 117 publications

(143 citation statements)

References 47 publications

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“…To further confirm the essential role of the rod domain and the dimerization of plectin in the recruitment of plectin to the NE, we made use of the MD-EBS-1 cell line (Geerts et al, 1999;Koster et al, 2004). These cells were established from a Journal of Cell Science 120 (19) patient with muscular dystrophy-associated epidermolysis bullosa simplex (MD-EBS), who was homozygous for an 8-base-pair duplication in exon 31 of plectin .…”

Section: Nesprin-3␣ Can Form Dimersmentioning

confidence: 99%

Requirements for the localization of nesprin-3 at the nuclear envelope and its interaction with plectin

Ketema

Wilhelmsen

Kuikman

et al. 2007

Journal of Cell Science

142

147

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The outer nuclear membrane proteins nesprin-1 and nesprin-2 are retained at the nuclear envelope through an interaction of their klarsicht/ANC-1/syne homology (KASH) domain with Sun proteins present at the inner nuclear membrane. We investigated the requirements for the localization of nesprin-3α at the outer nuclear membrane and show that the mechanism by which its localization is mediated is similar to that reported for the localization of nesprin-1 and nesprin-2: the last four amino acids of the nesprin-3α KASH domain are essential for its interaction with Sun1 and Sun2. Moreover, deletion of these amino acids or knockdown of the Sun proteins results in a redistribution of nesprin-3α away from the nuclear envelope and into the endoplasmic reticulum (ER), where it becomes colocalized with the cytoskeletal crosslinker protein plectin. Both nesprin-3α and plectin can form dimers, and dimerization of plectin is required for its interaction with nesprin-3α at the nuclear envelope, which is mediated by its N-terminal actin-binding domain. Additionally, overexpression of the plectin actin-binding domain stabilizes the actin cytoskeleton and prevents the recruitment of endogenous plectin to the nuclear envelope. Our studies support a model in which the actin cytoskeleton influences the binding of plectin dimers to dimers of nesprin-3α, which in turn are retained at the nuclear envelope through an interaction with Sun proteins.

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Section: Nesprin-3␣ Can Form Dimersmentioning

confidence: 99%

Requirements for the localization of nesprin-3 at the nuclear envelope and its interaction with plectin

Ketema

Wilhelmsen

Kuikman

et al. 2007

Journal of Cell Science

142

147

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“…A model for the spatial organization of hemidesmosome components has been proposed in which the two transmembrane proteins α6β4 integrin and BP180 are connected through plectin and BP230 to the intermediate filament system (Koster et al, 2003(Koster et al, , 2004. However, it is unknown how the different hemidesmosome components are spatially organized relative to one another.…”

Section: Introductionmentioning

confidence: 99%

The molecular architecture of hemidesmosomes as revealed by super-resolution microscopy

Nahidiazar

Kreft

Broek

et al. 2015

Journal of Cell Science

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Hemidesmosomes have been extensively studied with immunofluorescence microscopy, but owing to its limited resolution, the precise organization of hemidesmosomes remains poorly understood. We studied hemidesmosome organization in cultured keratinocytes with two-and three-color super-resolution microscopy. We observed that, in the cell periphery, nascent hemidesmosomes are associated with individual keratin filaments and that β4 integrin (also known as ITGB4) is distributed along, rather than under, keratin filaments. By applying innovative methods to quantify molecular distances, we demonstrate that the hemidesmosomal plaque protein plectin interacts simultaneously and asymmetrically with β4 integrin and keratin. Furthermore, we show that BP180 (BPAG2, also known as collagen XVII) and BP230 (BPAG1e, an epithelial splice variant of dystonin) are characteristically arranged within hemidesmosomes with BP180 surrounding a central core of BP230 molecules. In skin cross-sections, hemidesmosomes of variable sizes could be distinguished with BP230 and plectin occupying a position in between β4 integrin and BP180, and the intermediate filament system. In conclusion, our data provide a detailed view of the molecular architecture of hemidesmosomes in cultured keratinocytes and skin.

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“…The plakin domain of plectin and other plakins contain protein-protein interaction sites and they are important for the localization of plakins at junctional complexes. In plectin this region harbors binding sites for the integrin ␤4 subunit (24), the cytoplasmic domain of BPAG2 (25), ␤-dystroglycan (13), ␤-synemin (15), and the tyrosine kinase Fer (26). The central region consists of a coiled-coil rod domain that acts as a structural spacer of the protein-protein binding sites located in the N-and C-terminal regions and mediates homodimerization of plectin.…”

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confidence: 99%

The Structure of the Plakin Domain of Plectin Reveals a Non-canonical SH3 Domain Interacting with Its Fourth Spectrin Repeat

Ortega

Buey

Sonnenberg

et al. 2011

Journal of Biological Chemistry

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Plectin belongs to the plakin family of cytoskeletal crosslinkers, which is part of the spectrin superfamily. Plakins contain an N-terminal conserved region, the plakin domain, which is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. We have combined x-ray crystallography and small angle x-ray scattering (SAXS) to elucidate the structure of the central region of the plakin domain of plectin, which corresponds to the SR3, SR4, SR5, and SH3 domains. The crystal structures of the SR3-SR4 and SR4-SR5-SH3 fragments were determined to 2.2 and 2.95 Å resolution, respectively. The SH3 of plectin presents major alterations as compared with canonical Pro-rich binding SH3 domains, suggesting that plectin does not recognize Pro-rich motifs. In addition, the SH3 binding site is partially occluded by an intramolecular contact with the SR4. Residues of this pseudobinding site and the SR4/SH3 interface are conserved within the plakin family, suggesting that the structure of this part of the plectin molecule is similar to that of other plakins. We have created a model for the SR3-SR4-SR5-SH3 region, which agrees well with SAXS data in solution. The three SRs form a semi-flexible rod that is not altered by the presence of the SH3 domain, and it is similar to those found in spectrins. The flexibility of the plakin domain, in analogy with spectrins, might contribute to the role of plakins in maintaining the stability of tissues subject to mechanical stress.Plakins are a family of high molecular weight proteins that interconnect elements of the cytoskeleton and tether them to membrane-associated structures; hence, they are also known as cytolinkers (1-2). Mammalian plakins include desmoplakin, plectin, the bullous pemphigoid antigen 1 (BPAG1), 4 the microtubule actin crosslinking factor 1 (MACF1, also known as ACF7, trabeculin, or macrophin), envoplakin, periplakin, and epiplakin. Plakins are also present in invertebrates; Drosophila melanogaster has a single plakin gene named shortstop (also know as kakapo) that encodes at least two protein forms, Shot I and Shot II. Similarly, the only plakin gene in Caenorhabditis elegans, vab-10, encodes two variants VAB-10A and VAB-10B.Plectin is a highly versatile plakin that associates with intermediate filaments (3), microtubules (4), and actin fibers (5), and crosslinks these cytoskeletal networks (5-6). Plectin also connects intermediate filaments to membrane-associated complexes. In stratified epithelia such as the skin, plectin is localized at the hemidesmosomes, which are junctional complexes that link the intermediate filaments to the basement membrane, and links the integrin ␣6␤4 and the bullous pemphigoid antigen 2 (BPAG2, also known as type XVII collagen or BP180) to the cytokeratins (7-8). Plectin is also localized at the desmosomes (9), which mediate cell-cell contacts, and connects the nuclear envelope to the intermediate filaments by binding to the outer nuclear membrane protein nesprin-3␣ (10 -11). In st...

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Role of Binding of Plectin to the Integrin β4 Subunit in the Assembly of Hemidesmosomes

Cited by 117 publications

References 47 publications

Requirements for the localization of nesprin-3 at the nuclear envelope and its interaction with plectin

Requirements for the localization of nesprin-3 at the nuclear envelope and its interaction with plectin

The molecular architecture of hemidesmosomes as revealed by super-resolution microscopy

The Structure of the Plakin Domain of Plectin Reveals a Non-canonical SH3 Domain Interacting with Its Fourth Spectrin Repeat

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