LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction

• DOI: 10.1038/ncomms12188
• Publication Date: 2016-07-19T09:37:05Z
• Authors: Jay Penney; Kazuya Tsurudome; Edward H. Liao; Grant Kauwe; Lindsay Gray; Akiko Yanagiya; Mario R. Calderon; Nahum Sonenberg; A. Pejmun Haghighi
• Keywords: LRRK2; Postsynaptic density; Synaptic vesicle recycling

Abstract Parkinson’s disease gene leucine-rich repeat kinase 2 (LRRK2) has been implicated in a number of processes including the regulation mitochondrial function, autophagy and endocytic dynamics; nevertheless, we know little about its potential role synaptic plasticity. Here demonstrate that postsynaptic knockdown fly homologue LRRK2 thwarts retrograde, homeostatic compensation at larval neuromuscular junction. Conversely, overexpression either or human transgene induces retrograde enhancement presynaptic neurotransmitter release by increasing size ready pool vesicles. We show promotes cap-dependent translation identify Furin 1 as translational target, which is required for function LRRK2. As homeostasis plays fundamental ensuring normal stable our findings suggest aberrant may lead to destabilization neural circuits.