Chaperone-mediated autophagy (CMA) is a substrate-specific mode of lysosomal proteolysis, with multiple lines of evidence connecting its dysfunction to both ageing and disease. We have recently shown that CMA impairment through knock-down of the lysosomal receptor LAMP2A is detrimental to neuronal viability in vivo; however, it is not clear which subset of proteins regulated by the CMA pathway mediate such changes. In this study, we have manipulated CMA function through alterations of LAMP2A abundance in primary rat cortical neurons, to identify potential changes to the neuronal proteome occurring prior to neurotoxic effects. We have identified a list of proteins with significant, >2-fold change in abundance following our manipulations, of which PARK7/DJ-1 - an anti-oxidant implicated in hereditary forms of Parkinson's Disease (PD), and DPYSL2/CRMP-2 - a microtubule-binding phosphoprotein involved in schizophrenia pathogenesis - were both found to have measurable effects on neuronal homeostasis and phenotype. Taken together, this study describes alterations in the abundance of neuronal proteins involved in neuropsychiatric disorders upon CMA manipulation, and suggests that such alterations may in part be responsible for the neurodegeneration observed upon CMA impairment in vivo.
Pubmed ID: 30562574 RIS Download
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View all literature mentionsImaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
View all literature mentionsThis polyclonal targets
View all literature mentionsThis unknown targets Donkey Sheep IgG(H+L) CF555
View all literature mentionsThis polyclonal targets Dpysl2
View all literature mentionsThis unknown targets Donkey Sheep IgG(H+L) CF488A
View all literature mentionsThis polyclonal targets TUBG1, TUBG2
View all literature mentionsThis monoclonal targets Neuronal Class III beta-Tubulin (TUJ1) Purified
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets MAP-2
View all literature mentionsThis monoclonal targets beta-actin
View all literature mentionsThis polyclonal targets PARK7/DJ1
View all literature mentionsThis polyclonal targets PHB
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsCell line HeLa S3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsRattus norvegicus with name P77PMC from RGD.
View all literature mentionsLight cycler software for analysis of quatitative real time PCR
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets MAP-2
View all literature mentionsThis polyclonal targets PARK7/DJ1
View all literature mentionsThis unknown targets Donkey Sheep IgG(H+L) CF555
View all literature mentionsThis polyclonal targets
View all literature mentionsThis unknown targets Donkey Sheep IgG(H+L) CF488A
View all literature mentionsThis polyclonal targets Dpysl2
View all literature mentions