Loss of c-Jun N-terminal kinase-interacting protein-1 does not affect axonal transport of the amyloid precursor protein or Aβ production

Abstract

Disruption to axonal transport is an early pathological feature inAlzheimer's disease. The amyloid precursor protein (APP) is a key axonal transport cargo inAlzheimer's disease since perturbation of its transport increasesAPP processing and production of amyloid-β peptide (Aβ) that is deposited in the brains of Alzheimer's disease patients. APP is transported anterogradely through axons on kinesin-1 motors. One favouredroute for attachment of APP to kinesin-1 involvesthe scaffolding protein c-JunN-terminal kinase-interacting protein-1(JIP1), which has been shown to bind both APP and kinesin-1 light chain (KLC). However, direct experimental evidence to support a role of JIP1 in APP transport is lacking. Notably, the effect of loss of JIP1 onmovement of APP through axons of living neurons, and the impact of such loss on APP processing and Aβ production has not been reported. To address these issues, we monitored how siRNAmediated loss of JIP1 influenced transport of enhanced green fluorescent protein (EGFP)-tagged APP through axons and production of endogenous Aβ in living neurons. Surprisingly,we found that knockdown of JIP1 did not affect either APP transport or Aβ production. These results have important implications for our understanding of APP trafficking in Alzheimer's disease. © The Author 2013. Published by Oxford University Press. All rights reserved.