The Wnt pathway controls cell death engulfment, spindle orientation, and migration through CED-10/Rac

Autor: Steve J. Charette, Michael O. Hengartner, Ralf Schnabel, Günter Lochnit, Juan Cabello, Ufuk Günesdogan, Lukas J. Neukomm, Katharina Burkart
Přispěvatelé: University of Zurich, Cabello, J
Rok vydání: 2010
Předmět:
Frizzled
Apoptosis
ComputingMilieux_LEGALASPECTSOFCOMPUTING
Cell Biology/Cell Signaling
Apoptotic cell clearance
0302 clinical medicine
2400 General Immunology and Microbiology
Cell polarity
Biology (General)
10. No inequality
beta Catenin
Developmental Biology/Embryology
0303 health sciences
biology
General Neuroscience
High Mobility Group Proteins
Wnt signaling pathway
LRP6
2800 General Neuroscience
LRP5
10124 Institute of Molecular Life Sciences
rac GTP-Binding Proteins
3. Good health
Cell biology
DNA-Binding Proteins
Rac GTP-Binding Proteins
RNA Interference
General Agricultural and Biological Sciences
Signal Transduction
Research Article
Beta-catenin
QH301-705.5
Spindle Apparatus
1100 General Agricultural and Biological Sciences
Protein Serine-Threonine Kinases
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
1300 General Biochemistry
Genetics and Molecular Biology
Two-Hybrid System Techniques
Cell Biology/Cytoskeleton
Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins
030304 developmental biology
General Immunology and Microbiology
Membrane Proteins
Wnt Proteins
Developmental Biology/Cell Differentiation
biology.protein
570 Life sciences
030217 neurology & neurosurgery
Developmental Biology
Zdroj: PLoS Biology
Digital.CSIC. Repositorio Institucional del CSIC
instname
PLoS Biology, Vol 8, Iss 2, p e1000297 (2010)
Europe PubMed Central
DOI: 10.1371/journal.pbio.1000297
Popis: This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
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 β-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.
This work was supported by an EU Training and Mobility of Researchers (TMR) Research Network grant (to RS), the Junta de Castilla y Leon (CSI03A08) (to JC), the Swiss National Science Foundation, and the Roche Research Fund. SJC was supported by a fellowship from the Canadian Institutes of Health Research and MOH was supported by the Ernst Hadorn Foundation.
Databáze: OpenAIRE
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