Journal Article

Comparative Study of Human and Mouse Postsynaptic Proteomes Finds High Compositional Conservation and Abundance Differences for Key Synaptic Proteins

Grant, Seth G. N., Collins, Mark O., Choudhary, Jyoti S., van de Lagemaat, Louie N., Bayés, Àlex, Croning, Mike D. R.

2012

Overview

Direct comparison of protein components from human and mouse excitatory synapses is important for determining the suitability of mice as models of human brain disease and to understand the evolution of the mammalian brain. The postsynaptic density is a highly complex set of proteins organized into molecular networks that play a central role in behavior and disease. We report the first direct comparison of the proteome of triplicate isolates of mouse and human cortical postsynaptic densities. The mouse postsynaptic density comprised 1556 proteins and the human one 1461. A large compositional overlap was observed; more than 70% of human postsynaptic density proteins were also observed in the mouse postsynaptic density. Quantitative analysis of postsynaptic density components in both species indicates a broadly similar profile of abundance but also shows that there is higher abundance variation between species than within species. Well known components of this synaptic structure are generally more abundant in the mouse postsynaptic density. Significant inter-species abundance differences exist in some families of key postsynaptic density proteins including glutamatergic neurotransmitter receptors and adaptor proteins. Furthermore, we have identified a closely interacting set of molecules enriched in the human postsynaptic density that could be involved in dendrite and spine structural plasticity. Understanding synapse proteome diversity within and between species will be important to further our understanding of brain complexity and disease.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abundance / Adaptor proteins / Alzheimer's disease / Alzheimers disease / Animal cognition / Animal models / Animals / Biodiversity / Biology / Brain / Centrifugation, Density Gradient / Cerebral Cortex - cytology / Cerebral Cortex - metabolism / Chromatography, Gel / Clinical medicine / Comparative analysis / Comparative studies / Complexity / Conservation / Cortex / Dendritic spines / Dendritic structure / Density / Evolution / Evolution (Biology) / Evolutionary biology / Female / Fractionation / Gene expression / Genomes / Glutamatergic transmission / Humans / Kinases / Laboratories / Male / Mass spectrometry / Medicine / Mice / Mice, 129 Strain / Nerve Tissue Proteins - isolation & purification / Nerve Tissue Proteins - metabolism / Neurosciences / Neurotransmitter receptors / Post-Synaptic Density - metabolism / Postsynaptic density / Postsynaptic density proteins / Protein Interaction Maps / Proteins / Proteome - isolation & purification / Proteome - metabolism / Proteomes / Quantitative analysis / Receptors / Schizophrenia / Scientific imaging / Species / Species diversity / Species Specificity / Spine / Synapses / Synapses - metabolism / Tandem Mass Spectrometry / Trends