A NOVEL MATRIX METALLOPROTEINASE GENE (XMMP) ENCODING VITRONECTIN-LIKE MOTIFS IS TRANSIENTLY EXPRESSED IN XENOPUS-LAEVIS EARLY EMBRYO DEVELOPMENT

To study the role of matrix metalloproteinases (MMPs) in early vertebr ate development, we cloned cDNAs for six different MMPs from the frog Xenopus laevis embryos at different stages of development and describe here a novel MMP called XMMP. Xenopus XMMP has 604 amino acids includ ing a putative signal peptide of 22 residues. At the carboxyl-terminal end of the propeptide, XMMP has a 37-amino acid-long insertion domain containing a segment that is 38% identical with a rat vitronectin seq uence between residues 108-135, Following this domain is an RRKR motif , a putative cleavage site for intracellular activation by furin prote inases, XMMP lacks a proline-rich linker peptide, or hinge region, typ ically found in other MMPs between the catalytic domain and carboxyl-t erminal ''hemopexin/vitronectin-like'' domain. In XMMP, the carboxyl-t erminal domain is composed of four tandem repeats that are 21-33% iden tical to a sequence (residues 213-264) encoded by vitronectin exon-5, Interestingly, XMMP gene is transiently expressed during Xenopus embry o development, XMMP mRNA of 3.0 kilobase pairs was undetected in the b lastula stage embryo, induced in gastrula embryo, expressed in neurula embryo, and then down-regulated in pretailbud embryo, In comparison, other Xenopus MMP genes that we have cloned show a different developme ntal regulation. In blastula embryo, the only MMP gene expressed was f ound to be 92-kDa type IV collagenase, which was also expressed in the gastrula, neurula, and pretailbud embryos. Expression of stromelysin- 1, stromelysin-3, and two different membrane type-MMPs was first detec ted in the neurula and pretailbud embryos, These results suggest that MMPs and the novel XMMP reported here play a role in Xenopus early dev elopment.