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Publication : The endosomal protein sorting nexin 4 is a synaptic protein.

First Author  Vazquez-Sanchez S Year  2020
Journal  Sci Rep Volume  10
Issue  1 Pages  18239
PubMed ID  33106523 Mgi Jnum  J:304118
Mgi Id  MGI:6694510 Doi  10.1038/s41598-020-74694-6
Citation  Vazquez-Sanchez S, et al. (2020) The endosomal protein sorting nexin 4 is a synaptic protein. Sci Rep 10(1):18239
abstractText  Sorting nexin 4 (SNX4) is an evolutionary conserved protein that mediates recycling from endosomes back to the plasma membrane in yeast and mammalian cells. SNX4 is expressed in the brain. Altered protein levels are associated with Alzheimer's disease, but the neuronal localization and function of SNX4 have not been addressed. Using a new antibody, endogenous neuronal SNX4 co-localized with both early and recycling endosome markers, similar to the reported localization of SNX4 in non-neuronal cells. Neuronal SNX4 accumulated specifically in synaptic areas, with a predominant localization to presynaptic terminals. Acute depletion of neuronal SNX4 using independent short hairpin RNAs did not affect the levels of the transferrin receptor, a canonical SNX4 cargo. Quantitative mass spectrometry revealed that upon SNX4 knockdown the class of proteins involved in neurotransmission was the most dysregulated. This included integral membrane proteins at both the presynaptic and postsynaptic side of the synapse that participate in diverse synaptic processes such as synapse assembly, neurotransmission and the synaptic vesicle cycle. These data suggest that SNX4 is implicated in a variety of synaptic processes.
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