Cloning of three variants of type XVIII collagen and their expression patterns during Xenopus laevis development

Abstract

Xenopus laevis type XVIII collagen occurs in three variants, 22 + 1285 amino acid residues (signal peptide + mature protein), 23 + 1581 residues and 23 + 1886 residues in length, differing in their N-terminal non-collagenous domains. The region showing highest homology to mammalian counterparts is the C-terminal endostatin domain. All three variants are expressed, at different levels, during early and late stages of development, as demonstrated by reverse transcription-polymerase chain reaction. Whole-mount in situ hybridization shows that the short variant is expressed at high levels in the developing eye, the central nervous system, the otic vesicle, the head mesenchyme, the branchial arches and the pronephros, and at the boundaries between somites. The middle variant is expressed in the head mesenchyme, the branchial arches, the peripheral nervous system, the pronephros and the pronephric duct, and at the somite boundaries. The longest variant is weakly expressed in the head mesenchyme and branchial arches.

Expression of Collagen XVIII and Localization of Its Glycosaminoglycan Attachment Sites

“…Three of these sites carry GAGs, confirming that collagen XVIII is a proteoglycan (10). All three attachment sites and their adjacent amino acids were conserved in human, mouse, and Xenopus collagen XVIII (22), consistent with the notion that collagen XVIIIs from other species are also proteoglycans (21). The chick SG consensus sites 1-6 were reduced in human and mouse to 1 single site, suggesting an evolutionary pressure to maintain at least one SG site at this position of the protein.…”

“…Sites 2, 3, and 4 appear as a group of three SG residues separated by 3 and 7 residues, respectively. Sites 3, 7, and 8 are conserved between chick, Xenopus (22), mouse, and human (Fig. 1).…”

Blocking Wnt signaling by SFRP-like molecules inhibits in vivo cell proliferation and tumor growth in cells carrying active β-catenin

“…Variant 2 (V2) is a plasma protein produced mainly in the liver (Musso et al, 2001). Variant 3 (V3) is expressed at very low levels during Xenopus embryogenesis (Elamaa et al, 2002), in human fetal (Elamaa et al, 2003), normal adult and tumor liver tissues (Quelard et al, 2008), and is not detected in metastatic CRCs (Musso et al, 2001). Proteolytic processing of V3 releases V3Nter, an aminoterminal glycoprotein containing a frizzled CRD, which locates at the cell surface in cancer cells and matches the three-dimensional structures of frizzled 8 and SFRP-3 CRDs (Quelard et al, 2008).…”

Estudo da região promotora do gene do colágeno XVIII humano

“…Recentemente foi descrita a expressão de genes homólogos ao colágeno XVIII em Xenopus laevis e Caenorhabditis elegans (Ackley et al, 2001;Elamaa et al, 2002). Em X. laevis e C. elegans o gene do colágeno XVIII também possui 3 isoformas e a maior homologia com o gene de camundongo, 79% e 55% respectivamente, ocorre na porção C-terminal, no domínio da endostatina (Ackley et al, 2001;Elamaa et al, 2002).…”

“…Em X. laevis e C. elegans o gene do colágeno XVIII também possui 3 isoformas e a maior homologia com o gene de camundongo, 79% e 55% respectivamente, ocorre na porção C-terminal, no domínio da endostatina (Ackley et al, 2001;Elamaa et al, 2002). Hanai e col., 2002, mostraram, em modelo de embriogênese de X. laevis, que a endostatina é capaz de inibir a duplicação de eixos induzidos por β-catenina, suprimir a transcrição de genes regulados por via de sinalização Wnt e, estimular a degradação de formas selvagens e estáveis de β-catenina por uma nova via de degradação, que não a via clássica envolvendo glicogênio sintase quinase (GSK3).…”