Geach, TJ;
(2006)
Tolloid metalloproteases implicated in dorsal-ventral pattern and extra-cellular matrix activation in Xenopus laevis.
Doctoral thesis , UCL (University College London).
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Abstract
Tolloid (Tld) metalloproteases are zinc dependent extra-cellular endopeptidases that have numerous roles during embryonic development. All Tlds have a highly conserved N-terminal protease domain and an array of C terminal CUB and EGF-like domains thought to play a role in substrate interactions. In Xenopus laevis three members of the Tld family have been identified, BMP-1/Tld, Xolloid and Xolloid-related. All modulate dorsal-ventral patterning of the developing embryo by cleaving the dorsalising factor Chordin, preventing it from binding and inhibiting of the signalling molecule BMP-4. Biochemical studies of mammalian Tlds have identified a wide range of substrates, many involved in formation of the extra-cellular matrix. BMP-1/Tld is identical to pro-collagen C-proteinase, an enzyme that removes the C- terminal pro-peptide of procollagen types 1, 2 and 3, the N-terminal pro-peptide of procollagen type 11 and both the N- and C-terminal pro-peptides of procollagen type 5. It also activates lysyl-oxidase (lox), an enzyme that plays an essential role in collagen maturation. In addition, BMP-1 has been implicated in the proteolytic activation of biglycan, endorepellin, myostatin, osteoglycin and the a-3 and y-2 chains of Laminin-5. In this thesis I identify and describe the expression for Xenopus homologues of procollagen 3al, 5al, 5a2 and Hal, biglycan and a laminin ct-chain like gene. I have also identified three members of the lox family and characterise their role during early Xenopus development. In addition, using a domain deletion approach, I determine the C-terminal CUB domains of Xolloid that are required for cleavage of Chordin. Finally, I study the potential role of endodermin, which displays significant homology to ct-2 macroglobulin, as an inhibitor of Tld metalloproteases.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Tolloid metalloproteases implicated in dorsal-ventral pattern and extra-cellular matrix activation in Xenopus laevis |
| Identifier: | PQ ETD:593584 |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis. Images identifying individuals have been redacted or partially redacted to protect their identity. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1446246 |
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