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The endosomal protein sorting nexin 4 is a synaptic protein
Sonia Vazquez-Sanchez1, Miguel A Gonzalez-Lozano2, Alexarae Walfenzao1
1Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, The Netherlands.
Scientific Reports
|October 27, 2020
Summary
Sorting nexin 4 (SNX4) is a brain protein involved in synaptic function. SNX4 knockdown disrupts neurotransmission proteins, suggesting its role in synaptic processes.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Sorting nexin 4 (SNX4) is an evolutionarily conserved protein mediating endosomal recycling to the plasma membrane.
- SNX4 is expressed in the brain, and altered levels are linked to Alzheimer's disease.
- Neuronal localization and function of SNX4 remain largely uncharacterized.
Purpose of the Study:
- To investigate the neuronal localization of SNX4.
- To elucidate the function of SNX4 in neuronal cells.
- To understand SNX4's role in synaptic processes.
Main Methods:
- Utilized a novel antibody to detect endogenous neuronal SNX4.
- Examined SNX4 co-localization with endosomal markers.
- Performed SNX4 knockdown using short hairpin RNAs (shRNAs).
- Analyzed protein levels via quantitative mass spectrometry.
Main Results:
- Endogenous neuronal SNX4 localized to early and recycling endosomes, concentrating at presynaptic terminals.
- SNX4 depletion did not affect transferrin receptor levels, a known SNX4 cargo.
- Quantitative mass spectrometry revealed significant dysregulation of neurotransmission-related proteins upon SNX4 knockdown.
- Affected proteins included presynaptic and postsynaptic integral membrane proteins involved in synapse assembly, neurotransmission, and synaptic vesicle cycling.
Conclusions:
- SNX4 is localized to presynaptic terminals in neurons.
- SNX4's primary role in neurons may not involve canonical cargo like the transferrin receptor.
- SNX4 plays a significant role in regulating proteins crucial for synaptic function and neurotransmission.
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