Worm Breeder's Gazette 13(4): 63 (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.
| 1 | Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855. |
| 2 | University of Pittsburgh, Department of Biological Sciences, Pittsburgh, PA 15260. |
Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855. We are interested in characterizing the genes sma-2 , sma-3 ,and sma-4 because they may participate in a TGF-337 signal transduction pathway that includes daf-4 ,a TGF-337 superfamily receptor. All four of these genes are required for proper body size, and for the proper development of male sensory rays and spicules. We have used mosaic analysis to determine the requirements for daf-4 and sma-2 in establishing sensory ray identity. daf-4 is required cell autonomously in each ray neuroblast to determine the identity of the corresponding ray. This result is consistent with temperature shift experiments which showed that daf-4 activity is required during the lifetime of the ray neuroblasts (WBG 13(2), p.39). Similarly, sma-2 mosaics reveal a cell autonomous requirement for sma-2 activity in the ray neuroblasts. This result implies two conclusions: (1) the sma-2 gene product does not act as a diffusible factor influencing the identities of multiple neuroblasts, and (2) sma-2 does not act in neighboring cells that may signal to the neuroblasts. The requirement for sma-2 and daf-4 activities in the same cells suggests that sma-2 may be necessary to transduce the signal received by the daf-4 receptor. Similar mosaic studies of sma-3 and sma-4 are ongoing,. In the last gazette, we reported preliminary evidence of the cloning of sma-2 :the identification of a missense mutation in sma-2 ( e502 ).This result has now been confirmed by the presence of a small deletion in a nearby exon in sma-2 ( e1491 ).The predicted sma-2 product is a novel protein of about 400 amino acids. SMA-2 does not contain any significant hydrophobic stretches, suggesting that the protein is not secreted; this is consistent with its cell autonomous requirement in ray neuroblasts. Since the protein contains no recognizable protein motifs, we do not know what its biochemical function may be. Although SMA-2 is not related to any other proteins in the database, the genome sequencing consortium has now identified two additional predicted ORFs with homology to sma-2 These proteins contain two conserved domains, an N-terminal region of ~120 residues and a C-terminal region of ~200 residues, that are separated by a less well conserved proline-rich domain. The first sma-2 homolog that was found maps near the predicted location of sma-3 .We are therefore testing the hypothesis that sma-3 encodes this homolog. Finally, the most recently identified sma-2 homolog maps to a cosmid overlapping one which we had already shown could rescue a sma-4 mutant. Deletions that disrupt the coding region of this homolog also eliminate rescuing activity, showing that sma-4 does in fact encode a sma-2 homolog. These results suggest the intriguing hypothesis that sma-2 , sma-3 ,and sma-4 may define a novel family of signalling proteins that act downstream of a TGF-337 superfamily receptor.