New functional roles for non-collagenous domains of basement membrane collagens

Ortéga, Nathalie; Werb, Zena

doi:10.1242/jcs.00106

Cited by 198 publications

(150 citation statements)

References 138 publications

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“…In the wider context of tumor biology many lines of investigation have implicated collagen IV proteolysis both in tumor growth and angiogenic regulation (26,27). Our findings now reveal one of the most direct molecular links to date between collagen and a major tumor suppressor.…”

Section: Discussionmentioning

confidence: 53%

Interaction of Hydroxylated Collagen IV with the von Hippel-Lindau Tumor Suppressor

Grosfeld

Stolze

Cockman

et al. 2007

Journal of Biological Chemistry

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The von Hippel-Lindau tumor suppressor (pVHL) targets hydroxylated ␣-subunits of hypoxia-inducible factor (HIF) for ubiquitin-mediated proteasomal destruction through direct interaction with the hydroxyproline binding pocket in its ␤-domain. Although disruption of this process may contribute to VHL-associated tumor predisposition by up-regulation of HIF target genes, genetic and biochemical analyses support the existence of additional functions, including a role in the assembly of extracellular matrix. In an attempt to delineate these pathways, we searched for novel pVHL-binding proteins. Here we report a direct, hydroxylation-dependent interaction with ␣-chains of collagen IV. Interaction with pVHL was also observed with fibrillar collagen chains, but not the folded collagen triple helix. The interaction was suppressed by a wide range of tumor-associated mutations, including those that do not disturb the regulation of HIF, supporting a role in HIF-independent tumor suppressor functions.

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Section: Discussionmentioning

confidence: 53%

Interaction of Hydroxylated Collagen IV with the von Hippel-Lindau Tumor Suppressor

Grosfeld

Stolze

Cockman

et al. 2007

Journal of Biological Chemistry

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“…• Collagen II: fragment is a bone morphogenetic protein (BMP) antagonist 125,126 • Collagen IV α1-α6 noncollagenous-1 (NC1) domains are anti-angiogenic after cleavage 121,124,127 • Collagen 18 has an NC1 domain (endostatin), which is anti-angiogenic 121,128…”

Section: Box 2 Biological Consequences Of Mmp Proteolysismentioning

confidence: 99%

“…• Adipocyte maturation requires the replacement of the surrounding interstitial matrix with a basement membrane 148,149 *Reviewed in REFS [121][122][123][124] .…”

Section: Differentiationmentioning

confidence: 99%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

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2,589

2,180

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Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Despite intensive scrutiny in vitro, in cell culture and in animal models, the normal physiological roles of these extracellular proteases have been elusive. Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.The founding member of the matrix metalloproteinase (MMP) family, collagenase, was identified in 1962 by Gross and Lapiere, who found that tadpole tails during metamorphosis contained an enzyme that could degrade fibrillar collagen 1,2 . Subsequently, an interstitial collagenase, collagenase-1 or MMP1, was found in diseased skin and synovium 3 . In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775-Ile776 or Gly775-Lys776 in native type I, II or III collagen molecules 3,4 . Further research led to the discovery of a family of structurally related proteinases (23 in human, 24 in mice), now referred to as the MMP family.Interest in MMPs increased in the late 1960s and early 1970s following observations that MMPs are upregulated in diverse human diseases including rheumatoid arthritis and cancer. Importantly, high levels of MMPs often correlated with poor prognosis in human patients (reviewed in REF. 5 ). However, recent clinical data indicate that the relationship between § These authors contributed equally to this paper. Competing interests statementThe authors declare no competing financial interests. DATABASESThe following terms in this article are linked online to: Entrez Genome: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene DmMmp1 | DmMmp2 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMMPs and disease is not simple; for example, increased MMP activity can enhance tumour progression or can inhibit it (reviewed in REF. 6 ). This complex relationship between MMP expression and cancer has increased the basic and clinical interest in understanding MMP function in vivo, but it has also focused attention on MMPs and pathology, and relatively less attention has been focused on the normal roles of these enzymes. MMP proteolysisMMPs are members of the metzincin group of proteases, which are named after the zinc ion and the conserved Met residue at the active site 11,12 . Recent work has generated a unified peptidase nomenclature 13 Functions of MMP proteolysisHistorically, MMPs were thought to function mainly as enzymes that degrade structural components of the ECM. However, MMP proteolysis can create space for cells to migrate, can produce specific substrate-cleavage fragments with independent biological activity, can MMPs in bone modelling and remodellingBone is an important site of ongoing tissue remodelling during development...

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“…For example, LET-2 may contain a cryptic guidance cue that is exposed by MIG-17-dependent proteolysis or by suppressor let-2 mutations. Cryptic fragments of type IV collagen having angiogenic and anti-angiogenic activities have been described in mammals (22)(23)(24).…”

Section: Nid-1-dependent and -Independent Pathways Downstream Of Mig-17mentioning

confidence: 99%

MIG-17/ADAMTS controls cell migration by recruiting nidogen to the basement membrane in C. elegans

Kubota¹,

Ohkura

Tamai

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Mutations in the a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family of secreted proteases cause diseases linked to ECM abnormalities. However, the mechanisms by which these enzymes modulate the ECM during development are mostly unexplored. The Caenorhabditis elegans MIG-17/AD-AMTS protein is secreted from body wall muscle cells and localizes to the basement membrane (BM) of the developing gonad where it controls directional migration of gonadal leader cells. Here we show that specific amino acid changes in the ECM proteins fibulin-1C (FBL-1C) and type IV collagen (LET-2) result in bypass of the requirement for MIG-17 activity in gonadal leader cell migration in a nidogen (NID-1)-dependent and -independent manner, respectively. The MIG-17, FBL-1C and LET-2 activities are required for proper accumulation of NID-1 at the gonadal BM. However, mutant FBL-1C or LET-2 in the absence of MIG-17 promotes NID-1 localization. Furthermore, overexpression of NID-1 in mig-17 mutants substantially rescues leader cell migration defects. These results suggest that functional interactions among BM molecules are important for MIG-17 control of gonadal leader cell migration. We propose that FBL-1C and LET-2 act downstream of MIG-17-dependent proteolysis to recruit NID-1 and that LET-2 also activates a NID-1-independent pathway, thereby inducing the remodeling of the BM required for directional control of leader cell migration.ECM ͉ fibulin-1 ͉ organogenesis ͉ type IV collagen T he interaction between basement membranes (BMs) and migrating cells or the epithelial layer is a complicated but carefully controlled process that involves remodeling of the ECM. For example, the migration of border cells required for oogenesis and patterning of the early embryo in Drosophila melanogaster is accompanied by precise regulation of the synthesis and degradation of type IV collagen, laminin, and perlecan (1, 2). Fibronectin expression is required for branching morphogenesis of the submandibular salivary gland, lung, and kidney in mouse (3). However, the mechanisms of cell-ECM interactions and the roles of BMs in cell migration remain largely unknown.Gonadogenesis in the nematode Caenorhabditis elegans serves as a simple model system for elucidating the function of BMs in organ morphogenesis. The development of hermaphrodite gonads is regulated by the migration of gonadal distal tip cells (DTCs), which promote directional elongation of the gonad arms during the larval stages to form the U-shaped gonads found in adult animals (4, 5). Two secreted a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family metalloproteases, MIG-17 and GON-1, are involved in this process. GON-1 is required for DTC motility, whereas MIG-17 controls the direction of DTC movement but does not control DTC motility per se (6, 7). MIG-17 is expressed in the body wall muscles and is localized to the BM of the gonad surface, where it is required for DTC migration (7,8). It has been proposed that MIG-17 and GON-1 remodel BMs via prote...

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New functional roles for non-collagenous domains of basement membrane collagens

Cited by 198 publications

References 138 publications

Interaction of Hydroxylated Collagen IV with the von Hippel-Lindau Tumor Suppressor

Interaction of Hydroxylated Collagen IV with the von Hippel-Lindau Tumor Suppressor

Matrix metalloproteinases and the regulation of tissue remodelling

MIG-17/ADAMTS controls cell migration by recruiting nidogen to the basement membrane in C. elegans

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