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Publication : The Retromer Supports AMPA Receptor Trafficking During LTP.

First Author  Temkin P Year  2017
Journal  Neuron Volume  94
Issue  1 Pages  74-82.e5
PubMed ID  28384478 Mgi Jnum  J:256145
Mgi Id  MGI:6114586 Doi  10.1016/j.neuron.2017.03.020
Citation  Temkin P, et al. (2017) The Retromer Supports AMPA Receptor Trafficking During LTP. Neuron 94(1):74-82.e5
abstractText  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 Abeta 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.
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