Author/Editor		Šribar, Jernej
Title		Znotrajcelični vezavni proteini za amoditoksin in njihova možna vloga v procesu mevrotoksičnosti
Translated title		Intracellular ammodytoxin-binding proteins and their possible role in the process of neurotoxicity
Type		monografija
Place		Ljubljana
Publisher		Univeza v Ljubljani, Medicinska fakulteta
Publication year		2005
Volume		str. 77
Language		slo
Abstract		Ammodytoxin (Atx) is a presynaptically neurotoxic secretory phospholipase Az (sPLA2) from the venom of the long nosed viper (Vipera ammodytes ammodytes). The molecular mechanism of neurotoxicity of this and similar sPLA2s is poorly understood. It has been proposed that beside the enzymatic activity and internalisation these neurotoxins have to bind to specific receptors in the nerve terminals of motoneurons. On neuro-muscular preparations, these toxins interfere with synaptic vesicle recycling and finally block the release of acetylcholine into the synaptic cleft. The respiratory muscles are paralysed and the victim dies due to respiratory arrest. Using neurotoxic sPLA2s as a tool, numerous sPLA2 receptors have been discovered on the plasma membrane, as well as intracellularly and extracellularly. By discovering new intracellular Atx-binding proteins in the porcine nervous tissue we wanted to support the internalisation hypothesis of these and similar sPLA2 neurotoxins. In the demyelinated P2 fraction of the porcine cerebral cortex, two high-affinity Atxbinding proteins have been discovered in the past. R180 and R25. R180 was characterised as an M-type sPLA2 receptor (M-type PLA2R). The identity of R25 remains unknown but it was shown to bind only neurotoxic Atx and related mutants. R25 is an integral membrane protein and it is most likely localised to mitochondria. As such it represents the first intracellular membrane sPLA2-binding protein. R25 could be a perfect target for the toxin and perhaps the morphological changes on mitochondria, such as swelling and loss of internal structures, is in fact a consequence of the interaction of Atx with this receptor. (Abstract truncated at 2000 characters)
Descriptors		PHOSPHOLIPASES A VIPER VENOMS PROTEIN BINDING NEUROTOXINS CALMODULIN SWINE