Reference - Detail
|Author||Cabello J, Neukomm LJ, Günesdogan U, Burkart K, Charette SJ, Lochnit G, Hengartner MO, Schnabel R.|
|Title||The Wnt pathway controls cell death engulfment, spindle orientation, and migration through CED-10/Rac.|
Wnt signalling pathways have extremely diverse functions in animals, including induction of cell fates or tumours, guidance of cell movements during gastrulation, and the induction of cell polarity. Wnt can induce polar changes in cellular morphology by a remodelling of the cytoskeleton. However, how activation of the Frizzled receptor induces cytoskeleton rearrangement is not well understood. We show, by an in depth 4-D microscopy analysis, that the Caenorhabditis elegans Wnt pathway signals to CED-10/Rac via two separate branches to regulate modulation of the cytoskeleton in different cellular situations. Apoptotic cell clearance and migration of the distal tip cell require the MOM-5/Fz receptor, GSK-3 kinase, and APC/APR-1, which activate the CED-2/5/12 branch of the engulfment machinery. MOM-5 (Frizzled) thus can function as an engulfment receptor in C. elegans. Our epistatic analyses also suggest that the two partially redundant signalling pathways defined earlier for engulfment may act in a single pathway in early embryos. By contrast, rearrangement of mitotic spindles requires the MOM-5/Fz receptor, GSK-3 kinase, and beta-catenins, but not the downstream factors LIT-1/NLK or POP-1/Tcf. Taken together, our results indicate that in multiple developmental processes, CED-10/Rac can link polar signals mediated by the Wnt pathway to rearrangements of the cytoskeleton.
|MeSH||Animals Apoptosis / genetics Apoptosis / physiology* Caenorhabditis elegans* / cytology Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism High Mobility Group Proteins / genetics High Mobility Group Proteins / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism RNA Interference Signal Transduction / genetics Signal Transduction / physiology* Spindle Apparatus / metabolism* Two-Hybrid System Techniques Wnt Proteins / genetics Wnt Proteins / metabolism* beta Catenin / genetics beta Catenin / metabolism rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / metabolism*|
|WOS Category||BIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY|