Relative abundance of proteins mapped to the functional subnetwork of the cytoskeleton organization.

<p>A Impact of APP deletion. B Impact of the NexCre-cDKO. Change in abundance of more than ±10% is reflected by increasing sizes of nodes. The color code corresponds to the degree of up- (magenta) and downregulation (green). Nodes in yellow represent proteins with changes in abundance of less than ±10%. Abbreviations are the respective gene names of individual proteins as given in UniProt database and in the supplementary information <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004832#pcbi.1004832.s001" target="_blank">S1 Table</a>.</p

Relative abundance of proteins mapped to the functional subnetwork of calcium homeostasis.

<p>A Impact of APP deletion. B Impact of the NexCre-cDKO. Change in abundance of more than ±10% is reflected by increasing sizes of nodes. The color code corresponds to the degree of up- (magenta) and downregulation (green). Nodes in yellow represent proteins with changes in abundance of less than ±10%. Abbreviations are the respective gene names of individual proteins as given in UniProt database and in the supplementary information <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004832#pcbi.1004832.s001" target="_blank">S1 Table</a>.</p

The interactome of the native hippocampal PAZ core proteome.

<p>A Proteins grouped according to their localization (localization layout). B Community structure layout (function) of the network. The size of the rings corresponds to the respective number of proteins. The color code corresponds to the pie chart diagram (cf. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004832#pcbi.1004832.g001" target="_blank">Fig 1E</a>). C Impact of APP deletion on relative protein abundance mapped according to their localizations. D Impact of the APP-KO on relative protein abundance mapped according to the community structure. E Impact of the NexCre-cDKO on relative protein abundance mapped according to their localizations. F Impact of the NexCre-cDKO on relative protein abundance mapped according to the community structure. Change in abundance of more than ±10% is reflected by increasing sizes of nodes. The color code corresponds to the degree of up- (magenta) and downregulation (green). Nodes in yellow represent proteins with changes in abundance of less than ±10%. Each node (dot in the rings) within this network represents a protein and each edge (connection) represents a reported physical interaction between two proteins. Edges are bundled for clarity.</p

Relative abundance of proteins mapped to the functional subnetwork of the synaptic vesicle cycle.

<p>A Impact of APP deletion. B Impact of the NexCre-cDKO. Change in abundance of more than ±10% is reflected by increasing sizes of nodes. The color code corresponds to the degree of up- (magenta) and downregulation (green). Nodes in yellow represent proteins with changes in abundance of less than ±10%. Abbreviations are the respective gene names of individual proteins as given in UniProt database and in the supplementary information <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004832#pcbi.1004832.s001" target="_blank">S1 Table</a>.</p

Scheme illustrating the regulatory role of APP in a context-sensitive manner at the hippocampal PAZ. R, regulator; M, mediator, C, central player.

<p>Color code: magenta, upregulation (in APP-mutants); green, downregulation (in APP-mutants); yellow, unaltered.</p

Overview of the experimental design.

<p>A Workflow of subcellular fractionation and immunopurification of the native hippocampal PAZ. B Experimental outline of isobaric labeling of peptides with TMT⁶ and MS analysis by nano-high-pressure liquid chromatography (nHPLC-ESI). C Example of peptide signals (m/z) for the six reporter groups. D Differences in protein abundance of hippocampal PAZ constituents between APP-mutant and control. E Pie chart diagram of proteins attributed to the PAZ. F Scheme of a PPI network illustrating proteins (exemplarily designated as A-K) as nodes and edge betweeness. The thickness of the connections represents the importance of the respective edges for information flow within the network (edge betweenness). Change in abundance of more than ±10% is reflected by increasing sizes of nodes. The color code corresponds to the degree of up- (magenta) and downregulation (green). Nodes in yellow represent proteins with changes in abundance of less than ±10%. UF, upper fractions; LF, lower fractions; IP, immunopurification, MB, magnetic bead; PM, plasma membrane; SV, synaptic vesicle, SC, signaling cascade; CS, cytoskeleton; ME, metabolic enzymes; MI, mitochondria; O, others.</p

Relative abundance of proteins mapped to the subcommunity structure of the network.

<p>The size of the rings corresponds to the respective number of proteins. Communities were subdivided into functional clusters according to Fig 5. A Impact of APP deletion. B Impact of the NexCre-cDKO. Change in abundance of more than ±10% is reflected by increasing sizes of nodes. The color code corresponds to the degree of up- (magenta) and downregulation (green). Nodes in yellow represent proteins with changes in abundance of less than ±10%.</p

Subcommunity structure of the network based on Fig 3B.

<p>The color code corresponds to the pie chart diagram (cf. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004832#pcbi.1004832.g001" target="_blank">Fig 1E</a>). The size of the rings corresponds to the respective number of proteins. Communities (1–7) were subdivided into the following functional clusters (e.g. 1.1–1.12): 1.1 Calcium Signaling, 1.2 Presynaptic Membrane, 1.3 Exocytosis, 1.4 Cytoskeleton Organization, 1.5 Membrane Assembly, 1.6 G-Protein Signaling, 1.7 Organelle Transport, 1.8 Actin Organization, 1.9 Synapse Assembly, 1.10 Membrane Regulation, 1.11 Inhibitory Regulation, 1.12 Vesicle Priming, 2.1 Membrane Trafficking, 2.2 Vesicle Budding, 2.3 Endocytosis, 2.4 Proton Transport, 2.5 Phospholipid Metabolism, 2.6 Vesicle Organization, 2.7 Membrane Organization, 3.1 Electron Transport Chain, 3.2 Energy Metabolism, 3.3 Stress Defense, 4.1 Cellular Respiration, 4.2 Glycolysis, 4.3 Guanine Metabolism, 4.4 Glycerol Metabolism, 4.5 Mitochondrial Metabolism, 4.6 Mitochondrial Assembly, 5.1 Fatty Acid Catabolism, 5.2 Neurotransmitter Metabolism, 5.3 Amino Acid Catabolism, 5.4 Metabolism, 5.5 Fatty Acid Metabolism, 5.6 Mitochondrial Targeting, 6.1 Mitochondrial Protein Trafficking, 6.2 Heatshock Response, 6.3 Neuronal Regulation, 6.4 Protein Folding, 7 Functional Dynamics.</p