Worm Breeder's Gazette 13(4): 64 (October 1, 1994)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

More tolloid Homologs in the Worm.

Cathy Savage, Seo Hee Cho, Alyce L. Finelli, Richard W. Padgett

Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855.

Figure 1

  Members of the tolloid/ BMP-1 family of metalloproteases are thought to interact
with extracellular growth factors to regulate a variety of developmental events. In
particular, the Drosophila gene tolloid interacts with decapentaplegic (dpp), a member
of the TGF-337 superfamily. Similarly, vertebrate BMP-1 co-purifies with other BMPs
(bone morphogenetic proteins) that are related TGF-337-like ligands. Proteins in the
tolloid/BMP- 1 family share a similar structure: they contain a predicted
metalloprotease domain; EGF repeats; and CUB repeats, which are also found in blood
complement proteins. These proteases are thought to interact with other proteins
through the EGF and CUB repeats, and to regulate their activity through proteolysis.
  We have previously reported sequence analysis of the first C. elegans member of
this metalloprotease family (WBG 12(4), p.30), which we have called toh-1 (tollish).
Since then, the genome sequencing consortium has identified four more predicted
ORFs with sequence similarity to tolloid. We have therefore isolated and sequenced
cDNAs for these genes, to determine whether these new genes encode true members of
the tolloid/ BMP-1 family. One of the putative homologs displayed no protease
homology. The predicted structures of the other three homologs are summarized
below. Two of these, on the cosmids C05D11 and F42A10 ,contain related
metalloprotease domains, but none of the characteristic protein interaction motifs of
the tolloid/ BMP-1 family. Only one homolog, on the cosmid R151 ,was found to
contain an EGF repeat and a CUB repeat. We therefore propose the name toh-2 for
this gene. toh-2 represents a novel member of this family, because it contains repeats
(TSP repeats) found in thrombospondin, an extracellular matrix protein.
  The presence of these two tolloid homologs in the worm raises several interesting
  (1) Do these homologs act together in a TGF-337-like signal transduction pathway,
in separate pathways, or combinatorially with other, as yet unidentified, tolloid-like
  (2) What roles do these genes have in nematode development?
  (3) What is the function of the toh-2 thrombospondin repeats? Are there
homologs in other organisms that also contain these repeats?
  (see figure)

Figure 1