Type XIII Collagen Is Identified as a Plasma Membrane Protein

Abstract

The complete primary structure of the mouse type XIII collagen chain was determined by cDNA cloning. Comparison of the mouse amino acid sequences with the previously determined human sequences revealed a high identity of 90%. Surprisingly, the mouse cDNAs extended further in the 5 direction than the previously identified human clones. The 5 sequences contained a new in-frame ATG codon for translation initiation which resulted in elongation of the N-terminal noncollagenous domain by 81 residues. These N-terminal sequences lack a typical signal sequence but include a highly hydrophobic segment that clearly fulfills the criteria for a transmembrane domain. The sequence data thus unexpectedly suggested that type XIII collagen may be located on the plasma membrane, with a short cytosolic N-terminal portion and a long collagenous extracellular portion.These sequence data prompted us to generate antipeptide antibodies against type XIII collagen in order to study the protein and its subcellular location. Western blotting of human tumor HT-1080 cell extract revealed bands of over 180 kDa. These appeared to represent disulfide-bonded multimeric polypeptide forms that resolved upon reduction into 85-95-kDa bands that are likely to represent a mixture of splice forms of monomeric type XIII collagen chains. These chains were shown to contain the predicted N-terminal extension and thus also the putative transmembrane segment. Immunoprecipitation of biotinylated type XIII collagen from surface-labeled HT-1080 cells, subcellular fractionation, and immunofluorescence staining were used to demonstrate that type XIII collagen molecules are indeed located in the plasma membranes of these cells.The collagen family of proteins presently includes 19 types of collagen, and several additional proteins have collagen-like domains (1, 2). The collagens can be divided into two subgroups in terms of their structural and functional characteristics, the fibril-forming and the nonfibril-forming collagens. Members of the former group, i.e. types I-III, V, and XI, aggregate into prominent fibrillar structures in many collagen-containing tissues. These molecules are structurally homologous and characterized by a long, uninterrupted collagen triple helix. The other collagens are unable to form fibrils, and they show considerable diversity in structure, macromolecular organization, tissue distribution, and function. One common feature is that they all have one or more interruptions in the collagenous sequence. Several subfamilies can be distinguished among the nonfibril-forming collagens as follows: the network-forming collagens (types IV, VIII and X), fibril-associated collagens with interrupted triple helices (which include types IX, XII, XIV, XVI and XIX), a beaded filament-forming collagen (type VI), the family of types XV and XVIII collagens, and a collagen with a transmembrane domain (type XVII). The last mentioned collagen is distinct from the other family members, because it is not secreted into the extracellular matrix.Type XIII collagen is...

Collagenous Transmembrane Proteins: Recent Insights into Biology and Pathology*

“…Associated Diseases Collagen XIII-This transmembrane collagen has a small cytosolic domain and a large ectodomain rich in collagenous sequences (39). Apart from a 60-amino acid linker region, most of the ectodomain consists of three collagenous domains, COL1-3, and short non-collagenous interruptions, NC1-4.…”

Type XIII Collagen Forms Homotrimers with Three Triple Helical Collagenous Domains and Its Association into Disulfide-bonded Trimers Is Enhanced by Prolyl 4-Hydroxylase

“…These two nonfibrillar collagen types are not structurally homologous except that both have been predicted to have a transmembrane domain near their N terminus. Immunoprecipitation of biotinylated type XIII collagen from surface-labeled HT-1080 cells, subcellular fractionation, and immunofluorescence staining have been used to demonstrate that type XIII collagen molecules are indeed located in the plasma membranes of these cells (3). Type XIII collagen molecules are presumed to reside in the plasma membrane in a "type II" orientation with a cDNA-derived predicted structure consisting of a short N-terminal cytosolic domain, a single transmembrane domain, and a large, mainly collagenous ectodomain.…”

The Cell Adhesion Domain of Type XVII Collagen Promotes Integrin-mediated Cell Spreading by a Novel Mechanism

“…Among the 19 different collagen subtypes that have been identified, types XIII and XVII are the only transmembrane proteins (2,3). Type XVII collagen (BP180) is hemidesmosomal transmembrane protein that is mutated in junctional epidermolysis bullosa and is targeted by autoantibodies in blistering skin diseases (4 -6).…”