Uncovering Discrete Synaptic Proteomes to Understand Neurological Disorders

Proteomes
Yi-Zhi Wang, Jeffrey N Savas

Abstract

The mammalian nervous system is an immensely heterogeneous organ composed of a diverse collection of neuronal types that interconnect in complex patterns. Synapses are highly specialized neuronal cell-cell junctions with common and distinct functional characteristics that are governed by their protein composition or synaptic proteomes. Even a single neuron can possess a wide-range of different synapse types and each synapse contains hundreds or even thousands of proteins. Many neurological disorders and diseases are caused by synaptic dysfunction within discrete neuronal populations. Mass spectrometry (MS)-based proteomic analysis has emerged as a powerful strategy to characterize synaptic proteomes and potentially identify disease driving synaptic alterations. However, most traditional synaptic proteomic analyses have been limited by molecular averaging of proteins from multiple types of neurons and synapses. Recently, several new strategies have emerged to tackle the 'averaging problem'. In this review, we summarize recent advancements in our ability to characterize neuron-type specific and synapse-type specific proteomes and discuss strengths and limitations of these emerging analysis strategies.

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Citations

Jun 5, 2019·Proteomes·Kenneth R Williams, Angus C Nairn
Mar 13, 2020·Nature Reviews. Neuroscience·Annette C Dolphin, Amy Lee
May 3, 2021·Molecular & Cellular Proteomics : MCP·Charlotte A G H van Gelder, Maarten Altelaar
Jul 13, 2021·Frontiers in Cellular Neuroscience·Andres Di PaoloJosé Roberto Sotelo-Silveira
Jan 19, 2021·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Michael P VitekRebecca M Edelmayer

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Methods Mentioned

BETA
FACS
affinity purification
affinity purifications
proximity tagging
RNA-Seq

Software Mentioned

BioID

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