[Abstract Title]. - Society for Neuroscience

Topic: B.07.c. Synaptic integration
Support: NIH Grant MH074313
Stanley Medical Research Institute
Title: Synaptic proteome of entorhinal cortex in rhesus monkeys
Authors: N. S. TANNU, *S. E. HEMBY;
Physiol & Pharmacol, Wake Forest Univ. Sch. Med., Winston-Salem, NC
Abstract: The entorhinal cortex (EC) in the parahippocampal region is critical in acquisition,
consolidation and recovery of long-term memory traces. EC essentially acts as a „gatekeeper‟ for
the declarative memory system with compromises in functional integrity evident in
schizophrenia, Alzheimer‟s disease as well as temporal lobe epilepsy. While modulation of
synaptic architecture forms the basis of synaptic plasticity, dysregulation of synaptic structure
and function is a principal cellular substrate of the aforementioned disorders. In view of the
involvement of synaptic plasticity and signaling in physiologic as well as pathological states of
EC it is imperative to understand the normative abundance of proteins in the presynaptic fraction
(PSF) and the post-synaptic density (PSD). Therefore, the present study documents the relative
expression of proteins between PSF and PSD of EC by coupling the isobaric tag peptide labeling
(iTRAQ) to multidimensional liquid chromatography (MDLC) and matrix-assisted laser
desorption ionization-time of flight-time of flight tandem mass spectrometry (MALDI-TOF-
TOF, MS/MS). The results show that the PSF and PSD exhibit signature expression patterns of
proteins comprised of transporters, ion channels, neurotransmitter receptors, receptor-associated
scaffold proteins, cytoskeletal proteins, kinases and other enzymes as well as proteins involved
in neurotransmitter secretion and signaling. Various transporters (e.g. SNAP-25, Synapsin 1,
Sodium-dependent glutamate/aspartate transporter 1 and 2, Synaptic vesicle glycoprotein 2 A
and B, Syntaxin-1A, and Syntaxin-binding protein 1); ion channels (e.g. Phospholemman
precursor, Syntaxin-1B2, and Glycoprotein M6 A and B isoform 1); and enzymes (e.g. Enolase 2
and Tyrosine 3/tryptophan 5 -monooxygenase activation protein, zeta polypeptide) were found to
be highly expressed in the PSF of EC. At the same time the cytoskeletal proteins (e.g. Ankyrin-3,
tubulin α 6 and β [2A and 4] isoform); growth cone proteins (e.g. Brain acid soluble protein 1
and neural phosphoprotein B-50); and the transmembrane signaling modulators were highly
expressed in the PSD compared with the PSP. The current study documents the first proteomic
signature of the entorhinal cortex. This comprehensive knowledge of the protein composition of
the synapse offers promise to understand the synaptic mechanisms in physiology and
pathological states involving the EC.
Disclosures: N.S. Tannu, None; S.E. Hemby , None.
Poster