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. Author manuscript; available in PMC: 2015 Aug 1.
Published in final edited form as: Biochim Biophys Acta. 2013 Nov 10;1842(8):1273–1281. doi: 10.1016/j.bbadis.2013.11.005

Figure 1. Cell biological pathways implicated in LRRK2-associated pathobiology: intersection with ERK1/2 and Wnt signaling pathways.

Figure 1

Altered endosomal dynamics, increased protein translation by inhibition of repressor protein 4E-BP1, and increased mitophagy contribute to a state of autophagic/lysosomal stress. LRRK2 promotes increased intracellular calcium and activates ERK1/2-dependent autophagy and downregulation of dendritic mitochondria. LRRK2 and ERK1/2 also regulate microtubule dynamics by phosphorylation of tau, actin and α/β-tubulin. LRRK2 also triggers Wnt-β-catenin and ERK1/2-dependent changes in gene transcription. The autophagic, transcriptional and cytoskeletal effects of mutant LRRK2 expression contribute to ERK1/2-dependent neurite shortening, while altered endosomal/vesicular dynamics affect synaptic function. 4E-BP1: translation repressor protein; APC: Adenomatous polyposis coli; CK1:Casein kinase 1; Dvl:Dishevelled; eIF-4E: eukaryotic translation inition factor 4E; ERK1/2:Extra cellular-signal regulated kinase 1/2; ERM: Ezrin-Radixin-Moesin; GSK3β:Glycogen synthase kinase 2beta; LRP6: low density lipoprotein receptor-related protein 6; LRRK2:Leucine-rich repeat kinase 2; MT: Microtubule; β-cat: beta catenin