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Séminaire - Geoffrey Swanson“Modulation of kainate receptor structure and function by auxiliary Neto proteins”.

Abstract :


 Kainate receptors modulate excitatory and inhibitory throughout the central and peripheral nervous systems. The recent discovery of two auxiliary proteins for kainate receptors, known as Neuropilin and tolloid-like (Neto) proteins 1 and 2, have introduced unexpected complexity in current models for the molecular composition and function of neuronal kainate receptors.

That is, Neto proteins modulate nearly all aspects of kainate receptor function in vitro, and it remains unclear to what extent they act as auxiliary proteins in the nervous system. Further, the structural and mechanistic basis for their modulatory actions on kainate receptors is not well understood. In this seminar, I will discuss our initial structural studies that identify key domains on kainate receptors that are modulated by Neto proteins as well as evidence that Neto2 acts as a bone fide auxiliary protein for kainate receptors in primary sensory neurons.

Our objective in these studies is to resolve several fundamental gaps in our current understanding of the mechanistic basis for Neto modulation of kainate receptors and more clearly elucidate their role in shaping kainate receptor function in the central and peripheral nervous systems.

Selected publications

2014 publications

Psychiatric Risk Factor ANK3/Ankyrin-G Nanodomains Regulate the Structure and Function of Glutamatergic Synapses
Smith KR, Kopeikina KJ, Fawcett-Patel JM, Leaderbrand K, Gao R, Schürmann B, Myczek K, Radulovic J, Swanson GT, Penzes P.
Neuron. 2014 Oct 22;84(2):399-415.doi:10.1016/j.neuron.2014.10.010.
ISSN: 08966273

Stephen F. Heinemann (1939–2014)
Elgoyhen AB, Swanson GT, Mulle C.
Neuron. 2014 Oct;84(1):15-17.
PMID: 25401191 ISSN: 10974199

Modulation of ionotropic glutamate receptor function by vertebrate galectins
Copits BA, Vernon CG, Sakai R, Swanson GT.
Journal of Physiology. 2014 May 15;592(10):2079-2096.doi:10.1113/jphysiol.2013.269597.
ISSN: 00223751

Recent progress in neuroactive marine natural products
Sakai R, Swanson GT.
Natural Product Reports. 2014 Feb;31(2):273-309.doi:10.1039/c3np70083f.
PMID: 24430532 PMCID: PMC3955223 ISSN: 02650568

Scientific focus :

Research

Our research focuses predominantly on understanding physiological processes mediated by glutamate receptors, which are signaling proteins that respond to glutamate, the predominant excitatory neurotransmitter in the vertebrate central nervous system. Aberrant glutamate receptor signaling has been implicated in a number of pathological conditions, including epilepsy, schizophrenia and neuropathic pain; because these proteins are critical to brain function, they also are involved in most neurological diseases to varying degrees. Furthermore, modulation of glutamate receptors underlies models of learning and memory such as long-term potentiation and depression. The critical roles played by glutamate receptors in neurophysiological and neuropathological processes provide a strong impetus for understanding these fascinating molecules at many levels of stud