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"Our instruments and expertise to peek inside synapses are quite unique in the world"
 

Prof. Dr. A.B. (Guus) Smit
Head of the Department of Molecular and
Cellular Neurobiology
 

“Insight in the formation and change of synapses is crucial to both understanding the normal brain and the pathological brain.” Prof. Dr. Guus Smit analyzes synapses on the level of proteins.We can analyze all proteins in the synapse, in one batch we characterize and quantify several hundreds of proteins. “We aim to discover the gene products that determine individual differences in cognitive functioning associated with addiction proneness."

In 2001, Smit and collaborators from the NKI in Amsterdam gained a worldwide crucial advantage in the study of ion channels when they published the crystallographic 3D-structure of a homologue of the ligand binding domain of the nicotinic acetylcholine receptor. “For twenty years people had been trying to achieve this. We succeeded in crystallizing this membrane protein by focusing on a water soluble analogue.” Being the only available structural model for the cys-loop family of receptors, the AChBP structure is very suitable for rational drug design.

 
 

Publications:

Celie PH, van Rossum-Fikkert SE, van Dijk WJ, Brejc K, Smit AB, Sixma TK. Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron . 2004 Mar 25;41(6):907-14.

Adriani W, Spijker S, Deroche-Gamonet V, Laviola G, Le Moal M, Smit AB, Piazza PV. Evidence for enhanced neurobehavioral vulnerability to nicotine during periadolescence in rats. J Neurosci . 2003 Jun 1;23(11):4712-6.

Koksma JJ, van Kesteren RE, Rosahl TW, Zwart R, Smit AB , Luddens H, Brussaard AB. Oxytocin regulates neurosteroid modulation of GABA(A) receptors in supraoptic nucleus around parturition. J Neurosci. 2003 Feb 1;23(3):788-97.

Kamphuis W, Schneemann A, van Beek LM, Smit AB , Hoyng PF, Koya E. Prostanoid receptor gene expression profile in human trabecular meshwork: a quantitative real-time PCR approach. Invest Ophthalmol Vis Sci. 2001 Dec;42(13):3209-15.

Harel M, Kasher R, Nicolas A, Guss JM, Balass M, Fridkin M, Smit AB, Brejc K, Sixma TK, Katchalski-Katzir E, Sussman JL, Fuchs S. Harel M, Kasher R, Nicolas A, Guss JM, Balass M, Fridkin M, Smit AB, Brejc K, Sixma TK, Katchalski-Katzir E, Sussman JL, Fuchs S. Neuron. 2001 Oct 25;32(2):265-75.

van Kesteren RE, Syed NI, Munno DW, Bouwman J, Feng ZP, Geraerts WP, Smit AB. Synapse formation between central neurons requires postsynaptic expression of the MEN1 tumor suppressor gene. J Neurosci. 2001 Aug 15;21(16):RC161.

Koert CE, Spencer GE, van Minnen J, Li KW, Geraerts WP, Syed NI, Smit AB, van Kesteren RE. Functional implications of neurotransmitter expression during axonal regeneration: serotonin, but not peptides, auto-regulate axon growth of an identified central neuron. J Neurosci. 2001 Aug 1;21(15):5597-606.

Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van Der Oost J, Smit AB, Sixma TK. Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature. 2001 May 17;411(6835):269-76.

Smit AB, Syed NI, Schaap D, van Minnen J, Klumperman J, Kits KS, Lodder H, van der Schors RC, van Elk R, Sorgedrager B, Brejc K, Sixma TK, Geraerts WP. A glia-derived acetylcholine-binding protein that modulates synaptic transmission. Nature . 2001 May 17;411(6835):261-8.

Hermann PM, van Kesteren RE, Wildering WC, Painter SD, Reno JM, Smith JS, Kumar SB, Geraerts WP, Ericsson LH, Smit AB, Bulloch AG, Nagle GT. Neurotrophic actions of a novel molluscan epidermal growth factor. J Neurosci. 2000 Sep 1;20(17):6355-64.