Dierick H et al. (1999) Curr Top Dev Biol "Cellular mechanisms of wingless/Wnt signal transduction."

Dierick H, Bejsovec AM

[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.

Cuong Tran H et al. (2020) Mitochondrion "Mitochondrial unfolded protein-related responses across kingdoms: similar problems, different regulators."

Cuong Tran H, Van Aken O

[Mitochondrion, 2020]

Mitochondria are key components of eukaryotic cells, so their proper functioning is monitored via different mitochondrial signalling responses. One of these mitochondria-to-nuclear 'retrograde' responses to maintain mitochondrial homeostasis is the mitochondrial unfolded protein response (UPR^mt), which can be activated by a variety of defects including blocking mitochondrial translation, respiration, protein import or transmembrane potential. Although UPR^mt was first reported in cultured mammalian cells, this signalling pathway has also been extensively studied in the nematode Caenorhabditis elegans. In yeast, there are no published studies focusing on UPR^mt in a strict sense, but other unfolded protein responses (UPR) that appear related to UPR^mt have been described, such as the UPR activated by protein mistargeting (UPR^am) and mitochondrial compromised protein import response (mitoCPR). In plants, very little is known about UPR^mt and only recently some of the regulators have been identified. In this paper, we summarise and compare the current knowledge of the UPR^mt and related responses across eukaryotic kingdoms: animals, fungi and plants. Our comparison suggests that each kingdom has evolved its own specific set of regulators, however, the functional categories represented among UPR^mt-related target genes appear to be largely overlapping. This indicates that the strategies for preserving proper mitochondrial functions are partially conserved, targeting mitochondrial chaperones, proteases, import components, dynamics and stress response, but likely also non-mitochondrial functions including growth regulators/hormone balance and amino acid metabolism. We also identify homologs of known UPR^mt regulators and responsive genes across kingdoms, which may be interesting targets for future research.