Harterink, Martin et al. (2010) C. elegans: Development and Gene Expression, EMBL, Heidelberg, Germany "The Secreted-Frizzled Related Protein in C. elegans Wnt signaling"

Doan, Thang, Middelkoop, Teije, Korswagen, Hendrik C, Harterink, Martin

[C. elegans: Development and Gene Expression, EMBL, Heidelberg, Germany, 2010]

The Wnt family of secreted signaling proteins is responsible for important developmental and homeostatic processes throughout the animal kingdom. Importantly, its deregulation is implicated in several human pathologies, most notably cancer. Therefore Wnt signaling has to be carefully regulated. Secreted Frizzled-related Proteins (SFRPs) are thought to negatively regulate Wnt signaling by binding to the Wnt ligand, although other functions in Wnt signaling have also been reported. Furthermore, changed SFRP expression patterns are associated with human pathologies (1). Recent evidence suggests that SFRPs can also enhance the diffusion of Wnt ligand and expand their signaling range, when ectopically expressed in the Xenopus embryo (2). Since C. elegans only has one sfrp gene, it represents the perfect model to carefully analyze SFRP function in Wnt signaling as well as its effect on the Wnt gradient formation. Here we will present our current results. 1. Bovolenta et al, JCS, 2008 2. Mii and Taira, Development, 2009

Li XJ et al. (1997) International C. elegans Meeting "HOP-1 LOCUS ENCODES A NOVEL HOMOLOG OF HUMAN PRESENILINS IN C. ELEGANS"

Greenwald IS, Li XJ

[International C. elegans Meeting, 1997]

Presenilins have been implicated in early-onset familial Alzheimer's disease. The C. elegans SEL-12 protein is highly similar to human presenilins (1). It appears to be a bona fide presenilin, since human presenilins can substitute for SEL-12 presenilin in a C. elegans functional assay (2), and SEL-12 and human presenilins have a similar membrane topology (3,4). In humans, there are two known presenilins, PS1 and PS2 (5). Using BLAST, we identified another potential C. elegans presenilin on cosmid C18E3 that is 35% identical to SEL-12. The predicted protein encoded by C18E3.b is less similar in amino acid sequence to PS1 and PS2 (30% identity) than is SEL-12 (50% identity), and displays considerable differences in some transmembrane domains that are highly conserved among SEL-12, PS1 and PS2. C18E3.b therefore in principle could be related to, but may not function as, a presenilin. In order to assess the presenilin activity of C18E3.b, we examined the ability of a full-length cDNA we constructed to rescue the mutant phenotype of sel-12(ar171) when expressed under the control of sel-12 5' flanking region sequences. We found efficient rescue in this assay, indicating that C18E3.b is a bona fide presenilin. Because in this assay C18E3.b has been shown to function as a presenilin, we have named it hop-1, for homolog of presenilin 1. Currently, we are working on identifying mutations in the hop-1 gene. 1. Levitan, D. and Greenwald, I. (1995) Nature 377: 351-354. 2. Levitan, D. et al. (1996) PNAS 93: 14940-14944. 3. Li, X. and Greenwald, I. (1996) Neuron 17: 1015-1021. 4. Doan, A. et al. (1996) Neuron 17: 1023-1030. 5. Rogaev, E. et al. (1995) Nature 376: 775-778.