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'.