IDENTIFICATION AND CHARACTERIZATION OF A NOVEL COLLAGENASE IN XENOPUS-LAEVIS - POSSIBLE ROLES DURING FROG DEVELOPMENT

Matrix metalloproteinases (MMPs) participate in extracellular matrix r emodeling and degradation and have been implicated in playing importan t roles during organ development and pathological processes. Although it has been hypothesized for >30 years that collagenase activities are responsible for collagen degradation during tadpole tail resorption, none of the previously cloned amphibian MMPs have been biochemically d emonstrated to be collagenases. Here, we report a novel matrix metallo proteinase gene from metamorphosing Xenopus laevis tadpoles. In vitro biochemical studies demonstrate that this Xenopus enzyme is an interst itial collagenase and has an essentially identical enzymatic activity toward a collagen substrate as the human interstitial collagenase. Seq uence comparison of this enzyme to other known MMPs suggests that the Xenopus collagenase is not a homologue of any known collagenases but i nstead represents a novel collagenase, Xenopus collagenase-4 (xCol4, M MP-18). Interestingly, during development, xCol4; is highly expressed only transiently in whole animals, at approximately the time when tadp ole feeding begins, suggesting a role during the maturation of the dig estive tract. More improtantly, during metamorphosis, xCol4 is regulat ed in a tissue-dependent manner. High levels of its mRNA are present a s the tadpole tail resorbs. Similarly, its expression is elevated duri ng hindlimb morphogenesis and intestinal remodeling. In addition, when premetamorphic tadpoles are treated with thyroid hormone, the causati ve agent of metamorphosis, xCol4 expression is induced in the tail. Th ese results suggest that xCol4 may facilitate larval tissue degenerati on and adult organogenesis during amphibian metamorphosis.