Overlapping roles of JIP3 and JIP4 in promoting axonal transport of lysosomes in human iPSC-derived neurons

The dependence of neurons on microtubule-based motors for the movement lysosomes over long distances raises questions about adaptations that allow to meet these demands. Recently, JIP3/MAPK8IP3, a neuronally enriched putative adaptor between and motors, was identified as critical regulator axonal lysosome abundance. In this study, we establish human induced pluripotent stem cell (iPSC)-derived neuron model investigation transport maturation show loss JIP3 results in accumulation Alzheimer's disease-related amyloid precursor protein (APP)-derived Aβ42 peptide. We furthermore reveal an overlapping role homologous JIP4 gene transport. These cellular investigating relationship amyloidogenic APP processing more broadly demonstrate utility iPSC-derived neuronal biology pathology. [Media: see text]