The Wnt Frizzled Receptor MOM-5 Regulates the UNC-5 Netrin Receptor through Small GTPase-Dependent Signaling to Determine the Polarity of Migrating Cells


Cells are exposed to a multitude of environmental cues that are often eliciting additive, overlapping, or even conflicting inputs. How the information from multiple extracellular cues is integrated within the cell to generate distinct patterning is largely unknown. Netrin and Wnt signaling pathways are critical to multiple developmental processes and play key roles in normal development, as well as in malignancies. The involvement of these two signaling pathways in establishing cellular polarity is key to their ability to determine organ shape and to regulate cell and axon migration. Here, we reveal a regulatory link between the Wnt Frizzled receptor, MOM-5, and the Netrin receptor UNC-5. We present evidence showing that MOM-5/Frizzled signals through small GTPases to negatively regulate the UNC-5 Netrin receptor. This regulatory link enables the integration of Netrin and Wnt signaling pathways and facilitates their orchestrated function in mediating polarity of cell migration.


Vyšlo v časopise: The Wnt Frizzled Receptor MOM-5 Regulates the UNC-5 Netrin Receptor through Small GTPase-Dependent Signaling to Determine the Polarity of Migrating Cells. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005446
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1005446

Souhrn

Cells are exposed to a multitude of environmental cues that are often eliciting additive, overlapping, or even conflicting inputs. How the information from multiple extracellular cues is integrated within the cell to generate distinct patterning is largely unknown. Netrin and Wnt signaling pathways are critical to multiple developmental processes and play key roles in normal development, as well as in malignancies. The involvement of these two signaling pathways in establishing cellular polarity is key to their ability to determine organ shape and to regulate cell and axon migration. Here, we reveal a regulatory link between the Wnt Frizzled receptor, MOM-5, and the Netrin receptor UNC-5. We present evidence showing that MOM-5/Frizzled signals through small GTPases to negatively regulate the UNC-5 Netrin receptor. This regulatory link enables the integration of Netrin and Wnt signaling pathways and facilitates their orchestrated function in mediating polarity of cell migration.


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