Adolescent cocaine exposure regulated the mRNA expression of many genes involved
in Wnt signaling pathways. These signaling pathways can alter the morphology of
the actin cytoskeleton and participate in the remodeling of synaptic and
dendritic structures following exposure to drugs of abuse. Signaling by Wnt
molecules leads to the activation of transcription factors and target genes. In
the canonical Wnt pathway, dishevelled inhibits a kinase-associated scaffolding
complex (GSK3B, casein kinase, PP2A) that normally facilitates the degradation
of beta catenin. Free beta catenin translocates to the nucleus where it
activates the transcription of Wnt target genes. Dishevelled, as well as axon
guidance molecules, also induce changes in actin polymerization and cytoskeletal
proteins via the activation of Rho GTPases. The calcium-mediated Wnt signaling
pathway is controlled by the Wnt5 molecules and activates transcription of cell
surface proteins and cell adhesion molecules. Shown in green are upregulated
genes and shown in red are downregulated genes. Solid arrows show direct
interactions and dashed arrows denote signaling processes with intermediates not
shown. Abbreviations: CaLN, calmodulin; LEF, lymphoid enhanced binding factor;
PLC, phospholipase C; TAK1, Tgf beta activated kinase 1; TCF, t-cell
transcription factor; TGFBR1/2, transforming growth factor beta receptor 1/2.
For a detailed list of all other genes names see table 3.