Characterization of the astacin family of metalloproteases in C. elegans

Ja-On Park,Donald G Moerman,Marcus-Oliver Schupp,Frank Möhrlen,Richard Zapf,Harald Hutter,David L Baillie,Jie Pan,Robert Johnsen

doi:10.1186/1471-213x-10-14

Abstract

BackgroundAstacins are a large family of zinc metalloproteases found in bacteria and animals. They have diverse roles ranging from digestion of food to processing of extracellular matrix components. The C. elegans genome contains an unusually large number of astacins, of which the majority have not been functionally characterized yet.ResultsWe analyzed the expression pattern of previously uncharacterized members of the astacin family to try and obtain clues to potential functions. Prominent sites of expression for many members of this family are the hypodermis, the alimentary system and several specialized cells including sensory sheath and sockets cells, which are located at openings in the body wall. We isolated mutants affecting representative members of the various subfamilies. Mutants in nas-5, nas-21 and nas-39 (the BMP-1/Tolloid homologue) are viable and have no apparent phenotypic defects. Mutants in nas-6 and nas-6; nas-7 double mutants are slow growing and have defects in the grinder of the pharynx, a cuticular structure important for food processing.ConclusionsExpression data and phenotypic characterization of selected family members suggest a diversity of functions for members of the astacin family in nematodes. In part this might be due to extracellular structures unique to nematodes.

Highlights

Astacins are a large family of zinc metalloproteases found in bacteria and animals
A comparison with sequences of other nematodes like C. remanei, C. briggsae and B. malayi shows that the astacin family has undergone significant evolution within the nematodes
The genome of B. malayi, a human parasite not closely related to C. elegans, contains only 13 astacins

Summary

Introduction

Astacins are a large family of zinc metalloproteases found in bacteria and animals. They have diverse roles ranging from digestion of food to processing of extracellular matrix components. A second member of the family, bone morphogenetic protein 1 (BMP-1), was found in vertebrates as a bone-inducing factor [4,5], illustrating the range of physiological functions associated with these proteases. BMP-1 and its Drosophila homologues, Tolloid and Tolloid-like are among the best characterized members of the family (see [6] for a recent review). BMP-1/Tolloid is conserved in evolution and found even in cnidarians [7] In vertebrates it is involved in processing components of the extracellular matrix, most notably fibrillar collagens, where it acts as procollagen C-protease [8]. Cleavage of chordin by BMP-1 in the embryo leads to activation of the TGF-b

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