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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
HUMAN CORD-7 RIM-MUTATION ALTERS PRESYNAPTIC FUNCTION IN DROSOPHILA
Abstract number: P292
Heckmann1 *M., Paul1 *M., Gehring1 J., DiAntonio2 A., Kittel1,3 R.J., Langenhan1 T.
1Physiologie, Neurophysiologie, Wrzburg, Germany
2Washington University School, Molecular Biology and Pharmacology, St Louis, United States
3Rudolf Virchow Center for Experimental Biomedicine, Wrzburg, Germany
RIM (Rab3 interacting molecule) is a multidomain active zone (AZ) protein with an N-terminal Zinc-finger-domain, a PDZ domain, a C2A domain, a proline rich region, and a C-terminal C2B domain (Pernía-Andrade & Jonas 2011). It functions as a scaffold, helps to regulate synaptic vesicle release and is relevant for synaptic plasticity (Wang et al., 1997; Castillo et al., 2002). A missense mutation in the C2A domain (R844H) of the human RIM1 homolog was found in patients with autosomal dominant cone-rod dystrophy (CORD7) which suffer from blindness due to retinal degeneration and show increased verbal IQs as an indicator for enhanced cognitive abilities compared with healthy relatives (Sisodiya et al., 2007). To test the impact of this mutation on synaptic function and plasticity we generatedDrosophila melanogaster lines expressing different transgenic constructs. Wild-type RIM was compared to R915H-substituted RIM (equivalent to the human R844H mutation) as an untagged and an N-terminally EGFP-tagged version. The tag was used to determine whether both wild-type and mutant RIM variants localize to the presynaptic terminal. Focal recordings at neuromuscular junctions of male third instar larvae uncovered changes in amplitude, rise- and decay-times of AP-evoked postsynaptic currents indicating altered presynaptic function.
References
Castillo PE, Schoch S, Schmitz F, Südhof TC, Malenka RC. (2002) RIM1alpha is required for presynaptic long-term potentiation. Nature 415:327–30
Pernía-Andrade A, Jonas P. (2011) The multiple faces of RIM. Neuron 69:185–7
Sisodiya SM, Thompson PJ, Need A, Harris SE, Weale ME, Wilkie SE, Michaelides M, Free SL, Walley N, Gumbs C, Gerrelli D, Ruddle P, Whalley LJ, Starr J.M, Hunt DM, Goldstein DB, Deary IJ, Moore AT. (2007) Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation. J Med Genet 44:373–80
Wang Y, Okamoto M, Schmitz F, Hofmann K, Südhof TC. (1997) Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion. Nature 388:593–8
Supported by DFG grants to MH (HE 2621/4-2 & B27/SFB 581)& RJK (KI 1460/1-1)
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 204, Supplement 689 :P292