AMPA receptors get ‘pickled’


No comments posted yet


Slide 1

AMPA receptors get ‘pickled’ Alexander C. Jackson and Roger A. Nicoll Kevin Kawchak Chemistry 555 2/2/11

Slide 2

AMPA (2-Amino-3-(5-Methyl-3-oxo-1,2- oxazol-4-yl)Propanoic Acid) Also an agonist for AMPA Receptor. Glutamate: Primary excitatory molecule that activates the AMPA Receptor. AMPAR: AMPA Receptor: a ligand-gated cation channel that facilitates neurotransmitter dependent synaptic transmission.

Slide 3

Schwenk Proteomic Rat Research: Discovered two mammalian cornichon protein homologues: CNIH-2, CNIH-3; which are directly linked to AMPAR trafficking. Fruitfly and yeast discovery: The cornichon protein has been acknowledged as a cargo receptor necessary for export of Epidermal Growth Factor Receptor ligands from Endoplasmic Reticulum. Cornichon proteins have shown remarkable phylogenic conservation of function. However, these proteins showed no compelling relationship with AMPAR. CNIH proteins are widely distributed in human brain, similar to TARP: Present in principal neurons, interneurons, glial cells in hippocampus, neocortex Except not in cerebral granule cells (Only TARP -2 protein existence). Further Schwenk Research: *Spawned additional experimentation into CNIH protein Functionality with AMPARs and other TARPs.

Slide 4

Schwenk TARP/CNIH – AMPAR Relationship: 30% of AMPARs associated with TARPs 70% of AMPARs associated with CNIH Reviewers skeptical of dominant CNIH association Unresolved TARP/CNIH Relationships: Trafficking pathway exclusivity TARP/CNIH interchangeability Formation of ternary complexes Division of Labor AMPAR w/ CNIH location restricted to ER CNIH kainite efficiency Glutamate Affinity AMPAR kinetics affected by CNIH: CNIH has a more dramatic affect on deactivating and desensitizing AMPAR than the corresponding TARP. CNIH responsible for enhanced charge transfer.

Slide 5

AMPA receptors get ‘pickled’ Alexander C. Jackson and Roger A. Nicoll Kevin Kawchak Chemistry 555 2/2/11 Discussion

Slide 6

References Jackson, A. C.; Nicoll, R. A. AMPA receptors get ‘pickled’. Nature. 2009, 458, 585-586. Kawchak, K. M.S. Thesis, Eastern Michigan University, 2012.\cgi\viewcontent.cgi?article=1753&context=theses KRAS mutations: Tumor Growth. Migraines: Why Migraines Strike. Nature Publishing Group: Nature Reviews: Neuroscience. (accessed Jan 29, 2011). Schwenk, Jochen. et al. Functional Proteomics Identify Cornichon Proteins as Auxiliary Subunits Of AMPA Receptors. Science. 2009, 323, 1313-1319. Stern, Peter. AMPA Receptor Modulator. Sci Signal. 2009, 2, 92.

Summary: The effects of glutamate and AMPA on the AMPA receptor. CNIH and TARP proteins also investigated.

Tags: glutamate ampa ampar cnih tarp