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Overlapping roles of JIP3 and JIP4 in promoting axonal transport of lysosomes in human iPSC-derived neurons by Swetha Gowrishankar; Lila Lyons; Nisha Mohd Rafiq; Agnes Roczniak-Ferguson; Pietro De Camilli; Shawn M. Ferguson is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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

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

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

Author

Swetha Gowrishankar; Lila Lyons; Nisha Mohd Rafiq; Agnes Roczniak-Ferguson; Pietro De Camilli; Shawn M. Ferguson

Publisher

American Society for Cell Biology (ASCB)

Published

2021

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)