Alterations in the function of the retromer, a multisubunit protein complex that plays a specialized role in endosomal sorting, have been linked to Alzheimer's and Parkinson's diseases, yet little is known about the retromer's role in the mature brain. Using in vivo knockdown of the critical retromer component VPS35, we demonstrate a specific role for this endosomal sorting complex in the trafficking of AMPA receptors during NMDA-receptor-dependent LTP at mature hippocampal synapses. The impairment of LTP due to VPS35 knockdown was mechanistically independent of any role of the retromer in the production of Aβ from APP. Finally, we find surprising differences between Alzheimer's- and Parkinson's-disease-linked VPS35 mutations in supporting this pathway. These findings demonstrate a key role for the retromer in LTP and provide insights into how retromer malfunction in the mature brain may contribute to symptoms of common neurodegenerative diseases. VIDEO ABSTRACT.
Pubmed ID: 28384478 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets GluR1
View all literature mentionsThis monoclonal targets FLAG??
View all literature mentionsThis monoclonal targets VPS35
View all literature mentionsSoftware used for visualizing and graphing data, image processing, and programming. It is designed for use by scientists and engineers and supports large data sets, evenly spaced data, and various data import formats. The software includes a suite of image processing operations for image filtering, manipulation, and quantification and is completely programmable.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.129S7-Apptm1Dbo/J from IMSR.
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.129S7-Apptm1Dbo/J from IMSR.
View all literature mentions