Abstract
Remodeling of the extracellular matrix (ECM) is pivotal for various biological processes, including organ morphology and development. The Caenorhabditis elegans male tail has male-specific copulatory organs, the rays and the fan. Ray morphogenesis, which involves a rapid remodeling of the ECM, is an important model of morphogenesis, although its mechanism is poorly understood. ADAMTS (a disintegrin-like and metalloproteinase with thrombospondin type I motifs) is a novel metalloproteinase family that is thought to be an important regulator for ECM remodeling during development and pathological states. We report here that a new C. elegans ADAMTS family gene, adt-1, plays an important regulatory role in ray morphogenesis. Inactivation of the adt-1 gene resulted in morphological changes in the rays as well as the appearance of abnormal protuberances around the rays. In addition, mating ability was remarkably impaired in adt-1 deletion mutant males. Furthermore, we found that the green fluorescent protein reporter driven by the adt-1 promoter was specifically expressed throughout the rays in the male tail. We hypothesize that ADT-1 controls the ray extension process via remodeling of the ECM in the cuticle.
Highlights
ADAM1 is a family of genes with structural homology to snake metalloproteinases and disintegrins [1,2,3]
We designated this gene as adt-1 ((ADAMTS in C. elegans)
C. elegans ADT-1 shows overall homology to mouse ADAMTS-1 without any large gap, indicating that the domain organization of C. elegans ADT-1 is very similar to that of mouse ADAMTS-1. This sequence alignment revealed that, like mammalian ADAMTS family proteins, ADT-1 is composed of multiple functional domains, including proprotein, metalloproteinase, and disintegrin-like domains and TSP type I motifs (Fig. 2)
Summary
ADAM1 is a family of genes with structural homology to snake metalloproteinases and disintegrins [1,2,3]. ADAMTS-1 is an ADAM family protein with thrombospondin (TSP) type I motifs that was originally identified as a gene highly expressed in vivo in the colon 26 cachexigenic tumor [10]. Analyses of deletion mutants demonstrated that the spacing region of the C-terminal half, as well as the three TSP type I motifs, is responsible for the tight interaction of ADAMTS-1 with the ECM [12]. Our data demonstrating that ADAMTS-1 is able to form a covalent binding complex with ␣2-macroglobulin indicate that ADAMTS-1 is an active metalloproteinase [13]. These observations led us to predict that ADAMTS-1 functions through proteolysis of ECM molecules. These observations demonstrate that ADAMTS-1 is necessary for proper function of the female genital organs [25]
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