The Molecular Basis of Wnt/β-Catenin Signaling Pathways in Neurodegenerative Diseases

Figure 2

Noncanonical Wnt signaling. (a) In the planar cell polarity (PCP) pathway, Wnt binds to Fz independent of its LRP5/6 coreceptor and activates Dsh. The activated Dsh with the help of Daam1 activates Rac and Rho which in turn activate c-Jun-N-terminal kinase (JNK) and Rho kinase (ROCK), respectively. ROCK and JNK cause cytoskeletal changes that contribute to cell polarization. (b) In the Wnt/Ca²⁺ pathway, the signal is transduced by the binding of Wnt to Fz which activates Dsh. Dsh via phospholipase-C (PLC) activates inositol triphosphate (IP3) without the involvement of Daam1 like in PCP. This triggers the release of intracellular Ca²⁺ which in turn activates Ca²⁺/calmodulin-dependent protein kinase II (CamKII) and protein kinase C (PKC). This promotes the nuclear translocation of the nuclear factor of activated T cells (NFACT) and cAMP response element-binding protein (CREB) (not shown), which later binds to its target gene and regulates gene expression.

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