Abnormal adherence junctions in the heart and reduced angiogenesis in transgenic mice overexpressing mutant type XIII collagen

Sund, Malin; Ylönen, Riikka; Tuomisto, Anne; Sormunen, Raija; Tahkola, Jenni; Kvist, Ari-Pekka; Kontusaari, Sirpa; Autio–Harmainen, Helena; Pihlajaniemi, Taina

doi:10.1093/emboj/20.18.5153

Cited by 35 publications

(36 citation statements)

References 39 publications

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“…The phenotypes of collagen XIII transgenic mice are manifold. Muscle cell attachment to basement membranes is deficient in mice with collagen XIII lacking the cytosolic and transmembrane domains (40), and a deletion within the COL2 domain led to embryonic lethality due to placental or cardiovascular defects (41).…”

Section: Other Collagenous Transmembrane Proteins Andmentioning

confidence: 99%

Collagenous Transmembrane Proteins: Recent Insights into Biology and Pathology*

Franzke

Brückner

Bruckner‐Tuderman

2005

Journal of Biological Chemistry

151

138

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Section: Other Collagenous Transmembrane Proteins Andmentioning

confidence: 99%

Collagenous Transmembrane Proteins: Recent Insights into Biology and Pathology*

Franzke

Brückner

Bruckner‐Tuderman

2005

Journal of Biological Chemistry

151

138

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“…With its potentially very deep penetration into the matrix of the largely collagenous ectodomain in conjunction with its wide tissue distribution, we propose that it may be a unique source of mechanical strength in cell-matrix and some cell-cell adherence junctions. Indeed, expression of truncated ␣1(XIII) chain in transgenic mice led to abnormal adherence junctions in the intercalated discs of cardiomyocytes (49). Insect cells synthesizing recombinant type XIII collagen and keratinocytes endogenously synthesizing this molecule (10,32) shed the elongated ectodomain to some degree.…”

Section: Figmentioning

confidence: 99%

The Type XIII Collagen Ectodomain Is a 150-nm Rod and Capable of Binding to Fibronectin, Nidogen-2, Perlecan, and Heparin

Tu¹,

Sasaki²,

Snellman³

et al. 2002

Journal of Biological Chemistry

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Type XIII collagen consists of a short N-terminal intracellular domain, a transmembrane domain, and a collagenous ectodomain, and it is found at many sites of cell adhesion. We report on the characterization of recombinant type XIII collagen. The shed ectodomain was purified from insect cell culture medium and shown to form 240-kDa trimers with a T m of 42°C. Correct chain association into a triple-helical conformation was confirmed by limited pepsin digestion and CD spectroscopy. Rotary shadowing electron microscopy of the ectodomain revealed it to be a 150-nm rod with two flexible hinges separating 31-, 52-, and 68-nm portions. The rods represent the collagenous domains 1-3, and the hinges coincide with the non-collagenous domains 2 and 3. By using surface plasmon resonance analysis, the ectodomain showed interaction with immobilized fibronectin, nidogen-2, and perlecan with K D values in the nanomolar range. The binding sites of type XIII collagen for fibronectin were localized to the collagenous domains, whereas the binding activities for nidogen-2 and perlecan resided in the pepsin-sensitive portions of the ectodomain. Furthermore, the ectodomain bound significantly to heparin, which also inhibited shedding of the ectodomain in insect cell cultures. The results reveal that type XIII collagen is notably distinct in its structure compared with other cell-surface proteins, and the in vitro binding with fibronectin, heparin, and two basement membrane components is indicative of multiple cell-matrix interactions in which this ubiquitously expressed protein participates.Two of the 19 collagens described in vertebrates belong to the subgroup of transmembrane collagens, namely type XIII and the hemidesmosomal component, type XVII collagen (1-3). These two nonfibrillar collagens are not structurally homologous except that both have a transmembrane domain. The collagen superfamily also includes other transmembrane proteins that have short collagenous domains, namely the types I and II macrophage scavenger receptors; C1q, the first component of complement C1; a macrophage receptor with a collagenous structure; and the ectodysplasin-A family of proteins (1, 3, 4).Type XIII collagen molecules reside in the plasma membrane of cells in a type II orientation with a short N-terminal cytosolic domain, a single transmembrane domain, and a large, mainly collagenous ectodomain (5, 6). The N-terminal non-collagenous domain, NC1, 1 of the human protein encompasses a 38-residue cytosolic domain, a 23-residue transmembrane domain, and the first 60 residues of the non-collagenous extracellular sequences adjacent to the plasma membrane (5). The rest of the ectodomain contains three collagenous sequences, COL1-3, with sizes of 104, 172, and 235 residues, respectively, and non-collagenous domains, NC2-4, with sizes of 34, 22, and 18 residues (5). The precursor RNAs encoding human and mouse type XIII collagen are known to be subject to complex alternative splicing, and hence the sizes of the COL1, NC2, COL3, and NC4 domains in humans ca...

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“…leads to fetal lethality (35). In this case the mutant molecules remain attached to the plasma membrane, folding of the affected domain is likely to be impaired, and the mutant molecules may produce incorrect signals in the cell.…”

Section: Two Separate Coiled-coil Motifs In Type XIII Collagen 37596mentioning

confidence: 99%

Type XIII Collagen and Some Other Transmembrane Collagens Contain Two Separate Coiled-coil Motifs, Which May Function as Independent Oligomerization Domains

Latvanlehto¹,

Snellman²,

et al. 2003

Journal of Biological Chemistry

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Type XIII collagen is a homotrimeric transmembrane collagen composed of a short intracellular domain, a single membrane-spanning region, and an extracellular ectodomain with three collagenous domains (COL1-3) separated by short non-collagenous domains (NC1-4). Several collagenous transmembrane proteins have been found to harbor a conserved sequence next to their membrane-spanning regions, and in the case of type XIII collagen this sequence has been demonstrated to be important for chain association. We show here that this 21-residue sequence is necessary but not sufficient for NC1 association. Furthermore, the NC1 association region was predicted to form an ␣-helical coiled-coil structure, which may already begin at the membrane-spanning region, as is also predicted for the related collagen types XXIII and XXV. Interestingly, a second coiled-coil structure is predicted to be located in the NC3 domain of type XIII collagen and in the corresponding domains of types XXIII and XXV. It is found experimentally that the absence of the NC1 coiled-coil domain leads to a lack of disulfide-bonded trimers and misfolding of the membrane-proximal collagenous domain COL1, whereas the COL2 and COL3 domains are correctly folded. We suggest that the NC1 coiled-coil domain is important for association of the N-terminal part of the type XIII collagen ␣ chains, whereas the NC3 coiled-coil domain is implicated in the association of the C-terminal part of the molecule. All in all, we propose that two widely separated coiled-coil domains of type XIII and related collagens function as independent oligomerization domains participating in the folding of distinct areas of the molecule.Type XIII collagen is a type II transmembrane protein that is expressed in many tissues throughout development and adult life (1). It is located in focal adhesions of cultured fibroblasts and other cells and in adhesive structures of tissues such as the myotendinous junctions in muscle, intercalated discs in heart, and the cell basement membrane interphases (1, 2). The type XIII collagen ectodomain can bind to fibronectin, heparin, the basement membrane components nidogen-2 and perlecan, and the ␣ 1 -subunit of integrin (3-5). Due to its location at the tissue and cell level and its binding properties, it has been postulated that type XIII collagen is involved in cellular adhesion and migration.Type XIII collagen ␣ chains produced in a recombinant insect cell culture system have been shown to form homotrimers (6). The primary structure is composed of three collagenous domains (COL1 1 to COL3), which are flanked and interrupted by non-collagenous domains (NC1 to NC4). The short cytosolic domain and the transmembrane domain encompass about half of the NC1 domain, whereas the rest of the molecule forms the ectodomain, which is a rod of about 150 nm with two flexible hinges coinciding with the NC2 and NC3 domains (5). The primary structures of COL1, NC2, COL3, and NC4 can vary, on account of complex alternative splicing (7-10). It has been shown recently that ext...

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Abnormal adherence junctions in the heart and reduced angiogenesis in transgenic mice overexpressing mutant type XIII collagen

Cited by 35 publications

References 39 publications

Collagenous Transmembrane Proteins: Recent Insights into Biology and Pathology*

Collagenous Transmembrane Proteins: Recent Insights into Biology and Pathology*

The Type XIII Collagen Ectodomain Is a 150-nm Rod and Capable of Binding to Fibronectin, Nidogen-2, Perlecan, and Heparin

Type XIII Collagen and Some Other Transmembrane Collagens Contain Two Separate Coiled-coil Motifs, Which May Function as Independent Oligomerization Domains

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