G2Cdb - Documentation


Documentation: Synapse Proteomics

Protein Complexes
PSP Member ?
PSD Member ?
NRC Member ?
ARC Member ?
mGluR5-C Member ?

Other Structures
Clathrin Vesicle ?
Mitochondria ?

Background

These data are the results of several systematic studies which attempted to identify all the proteins present in the region of the synapse, and to specify both where in the synapse they were found and which protein families they belonged to.

Synapses are junctions between neurons. When a neuron is activated, an action potential travels along its axon to the axon terminal region. Its arrival triggers the release of neurotransmitters. The neurotransmitter molecules diffuse across the synaptic cleft and bind to receptors on another neuron. This has the effect of changing that neuron's probability of becoming activated; the neurotransmitters may have an excitatory or inhibitory effect.

The neurotransmitter receptors are known to be associated with a large number of proteins. Collectively, these proteins are known as the Post-Synaptic Proteome (PSP). The 'PSP Member ?' field indicates whether a given protein is a member of the PSP.

A crucial subset of the PSP is the Post-Synaptic Density (PSD). This is found in excitatory synapses of the central nervous system. It is a marked thickening in the cytoplasmic surface of the post-synaptic membrane. It is believed to have a wide range of crucial functions in the synapse, and is thought to be a key component in cognition. The 'PSD Member ?' field indicates whether a given protein is a member of the PSD. The PSD can be further sub-divided into multiprotein complexes.

One of the most widely-studied neurotransmitter receptors is the NMDA receptor. This is associated with a complex of over 100 proteins, known as the NMDA Receptor Complex or MAGUK-Associated Signalling Complex (NRC-MASC). These proteins are the main focus of study for the Genes to Cognition project. The 'NRC Member ?' field indicates whether a given protein has been found to be a member of the NRC-MASC.

Similarly, a second neurotransmitter of great interest is the AMPA receptor. This is associated with a group of proteins termed the AMPA Receptor Complex, or ARC. Collins et al's results suggest that this is a much smaller complex than the MASC. The 'ARC Member ?' field indicates whether a given protein has been found to be a member of the ARC.

Further neurotransmitter receptors of interest are the Metabotropic Glutamate Receptors. Several have been identified; one of the more widely investigated is mGluR5. The mGluR5-Signalling Complex has been found to contain 76 proteins. The 'mGluR5-C Member ?' field indicates whether a given protein has been found to be a member of the mGluR5-Signalling Complex.

Several other cellular structures are crucial for the correct functioning of synapses, in particular Clathrin Vesicles and Mitochondria. Clathrin vesicles are critical for the release of neurotransmitter from pre-synaptic neurones. Mitochondria are organelles which generate energy to power cell functions, for example through the oxidative phosphorylation pathway. The fields 'Clathrin Vesicle ?' and 'Mitochondria ?' specify whether a given protein has been found in these structures.

Figure 1: Overlap between multiprotein complexes in post-synaptic neurones

Protein Complexes

PSP Member ?
Is the protein a member of the Post-Synaptic Proteome (PSP)?

These data are taken from 16236029, 'Collins MO, Husi H, Yu L, Brandon JM, Anderson CN, Blackstock WP, Choudhary JS, Grant SG, "Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome", J Neurochem, 2005 Oct, 17'.


PSD Member ?
Is the protein a member of the Post-Synaptic Density (PSD)?

These data were obtained by Collins et al (2005). After carrying out their own study of the composition of the PSD, they collated six other studies which had also attempted to identify its constituent proteins. Proteins that had been reported more than once were considered to be of high confidence.

The study is described in 16236029, 'Collins MO, Husi H, Yu L, Brandon JM, Anderson CN, Blackstock WP, Choudhary JS, Grant SG, "Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome", J Neurochem, 2005 Oct, 17'.


NRC Member ?
Is the protein a member of the NMDA Receptor Complex (NRC)?

These data are taken from 16236029, 'Collins MO, Husi H, Yu L, Brandon JM, Anderson CN, Blackstock WP, Choudhary JS, Grant SG, "Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome", J Neurochem, 2005 Oct, 17'.

Figure 2: Protein-protein interactions within the NMDA Receptor Complex(NRC)

ARC Member ?
Is the protein a member of the AMPA Receptor Complex (ARC)?

These data are taken from 16236029, 'Collins MO, Husi H, Yu L, Brandon JM, Anderson CN, Blackstock WP, Choudhary JS, Grant SG, "Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome", J Neurochem, 2005 Oct, 17'.


mGluR5-C Member ?
Is the protein a member of the mGluR5-Signalling Complex?

These data are taken from 15447677, 'Farr CD, Gafken PR, Norbeck AD, Doneanu CE, Stapels MD, Barofsky DF, Minami M, Saugstad JA, "Proteomic analysis of native metabotropic glutamate receptor 5 protein complexes reveals novel molecular constituents", J Neurochem, 2004 Oct, 91(2), 438-50'.


Other Structures

Clathrin Vesicle ?
Is the protein present in brain clathrin-coated vesicles?

These data are taken from 15007177, 'Blondeau F, Ritter B, Allaire PD, Wasiak S, Girard M, Hussain NK, Angers A, Legendre-Guillemin V, Roy L, Boismenu D, Kearney RE, Bell AW, Bergeron JJ, McPherson PS, "Tandem MS analysis of brain clathrin-coated vesicles reveals their critical involvement in synaptic vesicle recycling", Proc Natl Acad Sci USA, 2004 Mar 16, 101(11), 3833-8. Epub 2004 Mar 8'.


Mitochondria ?
Is the protein present in mitochondria?

These data are taken from 14651853, 'Mootha VK, Bunkenborg J, Olsen JV, Hjerrild M, Wisniewski JR, Stahl E, Bolouri MS, Ray HN, Sihag S, Kamal M, Patterson N, Lander ES, Mann M, "Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria", Cell 2003 Nov 26, 115(5), 629-40'.



Documentation

Genetics
Plasticity
Plasticity References
Behaviour
Human Diseases
Proteomics
Plasticity Statistics
Total Genes1318
Plasticity Genes206
LTP Genes143
Plasticity References338
Disease Genes in NRC50
NRC Members186