Center for Neurogenomics and Cognitice Research
De Boelelaan 1085


1081 HV - Amsterdam
Netherlands

+31-(0)20-598 6936
+31-(0)20-598 6926
matthijs.verhage@cncr.vu.nl

Job opportunities

The Dept. of Functional Genomics at FALW of the VUA has been aiming at the solving the mechanisms underlying release of neurotransmitters from the synapse.
It is currently known that this requires the assembly of vesicle- and target-membrane-associated proteins (synaptobrevin, syntaxin and SNAP25), together forming the SNARE complex.
To identify the molecular interplay of the SNARE complex with other presynaptic proteins, the group Verhage characterized various other presynaptically expressed genes by genetic deletion in mice.
Among these a gene designated Munc18-1 (encoding a syntaxin-interacting protein) was identified to have an essential function in in vivo neurotransmission.
Worldwide, Munc18-1 deficient mice represent the first mouse model in which neurotransmitter secretion is completely abolished.
For this unique property, it is referred to as the silent mouse, and forms the basis for extensive international collaborations with top quality laboratories in neuroscience (e.g.
Thomas Südhof, Dallas, USA and Reinhard Jahn, Göttingen (Germany).

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Bochdanovits Z, Verhage M, Smit AB, de Geus EJ, Posthuma D, Boomsma DI, Penninx BW, Hoogendijk WJ, Heutink P. Joint reanalysis of 29 correlated SNPs supports the role of PCLO/Piccolo as a causal risk factor for major depressive disorder. Mol Psychiatry, 2009; 14(7): 650-652.

de Jong AP, Verhage M. Presynaptic signal transduction pathways that modulate synaptic transmission. Curr Opin Neurobiol. 2009; 19(3): 245-253.

de Wit H, Walter AM, Milosevic I, Gulyás-Kovács A, Riedel D, Sørensen JB, Verhage M. Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes. Cell, 2009; 138(5): 935-946.

de Wit J, Toonen RF, Verhage M. Matrix-dependent local retention of secretory vesicle cargo in cortical neurons. J Neurosci, 2009; 29(1): 23-37.

Gerber SH, Rah JC, Min SW, Liu X, de Wit H, Dulubova I, Meyer AC, Rizo J, Arancillo M, Hammer RE, Verhage M, Rosenmund C, Südhof TC. Conformational switch of syntaxin-1 controls synaptic vesicle fusion. Science, 2008; 321(5895): 1507-1510.

Gulyás-Kovács A, de Wit H, Milosevic I, Kochubey O, Toonen R, Klingauf J, Verhage M, Sørensen JB. Munc18-1: sequential interactions with the fusion machinery stimulate vesicle docking and priming. J Neurosci, 2007; 27(32): 8676-8686.

Sullivan PF, de Geus EJ, Willemsen G, James MR, Smit JH, Zandbelt T, Arolt V,  Baune BT, Blackwood D, Cichon S, Coventry WL, Domschke K, Farmer A, Fava M, Gordon SD, He Q, Heath AC, Heutink P, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hu Y, Kohli M, Lin D, Lucae S, Macintyre DJ, Maier W, McGhee KA, McGuffin P, Montgomery GW, Muir WJ, Nolen WA, Nöthen MM, Perlis RH, Pirlo K, Posthuma D, Rietschel M, Rizzu P, Schosser A, Smit AB, Smoller JW, Tzeng JY, van Dyck R, Verhage M, Zitman FG, Martin NG, Wray NR, Boomsma DI, Penninx BW. Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo. Mol Psychiatry. 2009; 14(4): 359-375.

Toonen RF, Kochubey O, de Wit H, Gulyas-Kovacs A, Konijnenburg B, Sørensen JB, Klingauf J, Verhage M. Dissecting docking and tethering of secretory vesicles at the target membrane. EMBO J, 2006; 25(16):3725-3737.

Toonen RF, Verhage M. Munc18-1 in secretion: lonely Munc joins SNARE team and takes control. Trends Neurosci, 2007; 30(11): 564-572. Review.

Toonen RF, Wierda K, Sons MS, de Wit H, Cornelisse LN, Brussaard A, Plomp JJ, Verhage M. Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size. Proc Natl Acad Sci U S A, 2006; 103(48): 18332-18337.

Verhage, M; Maia, AS; Plomp, JJ, et al. Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science, 2000, 287(5454): 864-869.

Verhage M, Sørensen JB. Vesicle docking in regulated exocytosis. Traffic, 2008; 9(9): 1414-1424. Review.

Verhage M, Toonen RF. Regulated exocytosis: merging ideas on fusing membranes. Curr Opin Cell Biol, 2007; 19(4): 402-408. Review.

Verhage M, van Meer G. Synaptobrevin, sphingolipids, and secretion: lube ´n´ go at the synapse. Neuron, 2009; 62(5): 603-605.

Wierda KD, Toonen RF, de Wit H, Brussaard AB, Verhage M. Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity. Neuron, 2007; 19; 54(2): 275-290.

Voets T, Toonen RF, Brian EC, de Wit H, Moser T, Rettig J, Südhof TC, Neher E, Verhage M. Munc18-1 promotes large dense-core vesicle docking. Neuron, 2001; 31(4): 581-591.