Alteration of endosomal trafficking is associated with early-onset parkinsonism caused by SYNJ1 mutations

• DOI: 10.1038/s41419-018-0410-7
• Publication Date: 2018-03-07T13:38:34Z
• Authors: Dominga Fasano; Silvia Parisi; Giovanna Maria Pi...; Anna De Rosa; Marina Picillo; Giuseppina Amodio; Maria Teresa Pell...; Paolo Barone; Ornella Moltedo; Vincenzo Bonifati; Giuseppe De Michele; Lucio Nitsch; Paolo Remondelli; Chiara Criscuolo; Simona Paladino
• Keywords: Transferrin receptor; Ectopic expression

Abstract Recently, a new form of autosomal recessive early-onset parkinsonism (PARK20), due to mutations in the gene encoding phosphoinositide phosphatase, Synaptojanin 1 (Synj1), has been reported. Several genes responsible for hereditary forms Parkinson’s disease are implicated distinct steps endolysosomal pathway. However, nature and degree endocytic membrane trafficking impairment remains elusive. Here, we show that depletion Synj1 causes drastic alterations early endosomes, which become enlarged more numerous, while it does not affect morphology late endosomes both non-neuronal neuronal cells. Moreover, loss impairs recycling transferrin, alter epidermal growth factor receptor. The ectopic expression restores functions rescues these defects depleted Importantly, same endosomal compartments occur fibroblasts PARK20 patients. Our data indicate plays crucial role regulating homeostasis different cell types, highlight defective cellular pathways PARK20. In addition, they strengthen link between disease.