[
Pflugers Arch,
2008]
The epithelial Na(+) channel (ENaC) is the rate-limiting step for Na(+) absorption in various vertebrate epithelia and deeply enmeshed in the control of salt and water homeostasis. The phylogenetic relationship of ENaC molecules to mechano-sensitive Degenerins from Caenorhabditis elegans indicates that ENaC might be mechano-sensitive as well. Primarily, it was suggested that ENaC might be activated by membrane stretch. However, this issue still remains to be clarified because controversial results were published. Recent publications indicate that shear stress represents an adequate stimulus, activating ENaC via increasing the single-channel open probability. Basing on the experimental evidence published within the past years and integrating this knowledge into a model related to the mechano-sensitive receptor complex known from C. elegans, we introduce a putative mechanism concerning the mechano-sensitivity of ENaC. We suggest that mechano-sensitive ENaC activation represents a nonhormonal regulatory mechanism. This feature could be of considerable physiological significance because many Na(+)-absorbing epithelia are exposed to shear forces. Furthermore, it may explain the wide distribution of ENaC proteins in nonepithelial tissues. Nevertheless, it remains a challenge for future studies to explore the mechanism how ENaC is controlled by mechanical forces and shear stress in particular.
[
Curr Top Dev Biol,
1999]
Wg/Wnt signaling regulates cell proliferation and differentiation in species as divergent as nematodes, flies, frogs, and humans. Many components of this highly conserved process have been characterized and work from a number of laboratories is beginning to elucidate the mechanism by which this class of secreted growth factor triggers cellular decisions. The Wg/Wnt ligand apparently binds to Frizzled family receptor molecules to initiate a signal transduction cascade involving the novel cytosolic protein Dishevelled and the serine/threonine kinase Zeste-white 3/GSK3. Antagonism of Zw3 activity leads to stabilization of Armadillo/beta-catenin, which provides a transactivation domain when complexed with the HMG box transcription factor dTCF/LEF-1 and thereby activates expression of Wg/Wnt-responsive genes. The Wg/Wnt ligands pass through the secretory pathway and associate with extracellular matrix components; recent work shows that sulfated glycosaminoglycans are essential for proper transduction of the signal. Mutant forms of Wg in Drosophila reveal separable aspects of Wg function and suggest that proper transport of the protein across cells is essential for cell fate specification. Complex interactions with the Notch and EGF/Ras signaling pathways also play a role in cell fate decisions during different phases of Drosophila development. These many facets of Wg/Wnt signaling have been elucidated through studies in a variety of species, each with powerful and unique experimental approaches. The remarkable conservation of this pathway suggests that Wg/Wnt signal transduction represents a fundamental mechanism for the generation of diverse cell fates in animal embryos.
[
Cell Biol Int,
2001]
This review discusses examples of conserved cellular and molecular mechansims in development, including the pathway of signal transduction between the photoreceptors R8 and R7 in Drosophila, which is compared to vulval induction in Caenorhabditis elegans. The Wg pathway in Drosophila is compared, first, to the Wnt pathway in dorsal mesoderm specification in Xenopus: second, to the same pathway in sea urchins; third, to the equivalent in the mom cascade of C. elegans; and finally, to parts of the equivalent pathway in Dictyostelium discoideum. The conserved expression of some hox genes in vertebrate limb buds and in the heads or tails of several invertebrate and vertebrate embryos is also illustrated. Two further examples show the contrast between BMP4 and the proteins Noggin, Chordin, Follistatin and Gremlin. Another example concerns the binding of proteins to the 3''UTRs of several messages which inhibits their translation in Drosophila and C. elegans. The final example illustrates the selective transfer of transcription factors to nuclei in Drosophila and C. elegans.