Wnt7b through Frizzlled-7 receptor regulates dendrite development by activation of CAMKII.

AYMARÁ RUFFINO; MARÍA EDITH FERRARI ; SILVANA ROSSO

Huerta Grande

Congreso; XXVII Congreso Annual de la Sociedad Argentina de Investigación en Neurociencia.; 2012

Sociedad Argentina de Investigación en Neurociencia.

Wnts are glycolipoproteins that signal through different receptors as Frizzleds, RYK and ROR2 to modulate intracellular events. Binding of Wnts to their receptors activates three cascades: Wnt/β-catenin, planar cell polarity and calcium pathways. In the nervous system, Wnt proteins regulate neuronal connectivity by controlling axon pathfinding, dendrite morphogenesis and synapses. In this study, we try to identify the Wnt7b receptor and the role of CaMKII in dendritic development. Our findings suggest that Wnt7b interacts with Frizzled-7 and this interaction increases the complexity of dendrites. In addition, this effect is blocked when neurons express the CRD-Fz7 or a shRNA-Fz-7. These evidences suggest that Fz7 may act as a receptor of Wnt7b to regulate dendrite morphogenesis. To go further, we examine the Wnt-Fz signaling involved in dendritogenesis. We observe that neurons exposed to Wnt show an increase in the level of phospho-CaMKII. This effect is blocked when neurons are treated with Sfrp1, a secreted Wnt antagonist. Furthermore, treatment with KN-93, a specific CaMKII inhibitor, abolishes the effects of Wnt7b on dendrite growth. Taken together, our results indicate that Wnt7b-Fz7 signaling is critical to regulate dendritic development through the activation of CaMKII.