Molecular mechanisms of glycine transporter GlyT2 mutations in startle disease
- James, Victoria M.
- Gill, Jennifer L.
- Topf, Maya
- Harvey, Robert J.
1Department of Pharmacology, The School of Pharmacy, London, WC1N 1AX, UK
2Institute of Structural and Molecular Biology/ Crystallography, Birkbeck College, London WC1E 7HX, UK
* Corresponding author
e-mail: [email protected]
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Victoria James graduated from Aston University, Birmingham with a Human Biology BSc (Hons) in 2005. She then went on to work as an Assay Scientist at Unipath in Bedford, while also completing her MSc in Molecular Medicine at Cranfield University. Now a PhD student in London at the School of Pharmacy and Birkbeck College, her work is centered on the discovery of mutations in genes that cause startle disease in humans and other species, combined with computational study of the structures of the proteins of the glycinergic inhibitory synapse that are involved in the mechanisms of this rare disease.
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Jennifer Gill graduated from the University of Aberdeen with a degree in Pharmacology in 2003. She then went on to work as a Research Assistant at the Roslin Institute in Edinburgh before completing a PhD in quantitative genetics at the University of Edinburgh. In 2010, she joined the Harvey lab in the Department of Pharmacology at The School of Pharmacy where she was responsible for investigating numerous startle-related neurological disorders in humans, cattle and dogs.
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Maya Topf obtained her BSc in Chemistry from Tel Aviv University in 1997 and a MSc in Computational Chemistry in 1999. She then moved to Oxford University where she obtained her DPhil in Physical Chemistry (2003). From 2003 to 2006, she worked as a postdoctoral fellow at the University of California San Francisco and following that she became a Medical Research Council Career Development Fellow at the Institute of Structural and Molecular Biology, Birkbeck/UCL, University of London. Her main research interests include the development and application of methods in computational biology to characterise the structure and function of macro-molecular assemblies.
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Robert J. Harvey obtained his BSc (Hons) in Biology from the University of York in 1987 and his PhD in Natural Sciences (Biochemistry) from the University of Cambridge in 1991. Following postdoctoral studies at the Institute for Cell biology and Clinical Neurobiology, Hamburg (1991-1996) and the Max-Planck-Institute for Brain Research, Frankfurt (1996-1998), he moved to the School of Pharmacy, London as a Lecturer in 1998. He is currently a Professor of Molecular Neuroscience and Genetics in the Department of Pharmacology. His major research interest is study the biology of inhibitory glycinergic and GABAergic neurotransmission in health and disease, using molecular biology and genetics techniques.
Received October 22, 2011; accepted November 17, 2011
Abstract
Startle disease affects newborn children and involves an exaggerated startle response and muscle hypertonia in response to acoustic or tactile stimuli. The primary cause of startle disease is defective inhibitory glycinergic transmission due to mutations in the postsynaptic glycine receptor (GlyR) α1 subunit gene (GLRA1). However, mutations have also been discovered in the genes encoding the GlyR β subunit (GLRB) and the presynaptic glycine transporter GlyT2 (SLC6A5). GlyT2 mutations have also been detected in Belgian Blue cattle and Irish Wolfhounds, where they have significant economic and animal welfare impacts.