1,335 research outputs found
SPARring with spines
No full textSynaptic plasticity underlies many essential processes in the brain, including learning and memory. In their perspective, Meyer and Brose discuss new work (Pak and Sheng) that elucidates one possible mechanism of use-dependent synaptic plasticity in neurons. This mechanism involves the Snk kinase-induced degradation of the SPAR protein leading to alterations in the morphology of postsynaptic dendritic spine
For better or for worse : Complexins regulate SNARE function and vesicle fusion
No full textIn contrast to constitutive secretion, SNARE-mediated synaptic vesicle fusion is controlled by multiple regulatory proteins, which determine the Ca(2+) sensitivity of the vesicle fusion process and the speed of excitation-secretion coupling. Complexins are among the best characterized SNARE regulators known to date. They operate by binding to trimeric SNARE complexes consisting of the vesicle protein synaptobrevin and the plasma membrane proteins syntaxin and SNAP-25. The question as to whether complexins facilitate or inhibit SNARE-mediated fusion processes is currently a matter of significant controversy. This is mainly because of the fact that biochemical experiments in vitro and studies on vertebrate complexins in vivo have yielded apparently contradictory results. In this review, I provide a summary of available data on the role of complexins in SNARE-mediated vesicle fusion and attempt to define a model of complexin function that incorporates evidence for both facilitatory and inhibitory roles of complexins in SNARE-mediated fusion
All Roads Lead to Neuroscience: The 2013 Nobel Prize in Physiology or Medicine
No full textNumerous metaphors have been employed to describe the achievements of the 2013 Nobel Laureates in Physiology or Medicine, James E. Rothman, Randy W. Schekman, and Thomas C. Südhof, who were honored for “their discoveries of machinery regulating vesicle traffic, a major transport system in our cells.” Most of these metaphors referred to the mundane issue of business logistics, and there is probably no other cell type in which the logistics problem is more pressing than in neurons
Synaptogenic proteins and synaptic organizers : "Many hands make light work"
No full textSynaptogenesis is thought to be mediated by cell adhesion proteins, which induce the initial contact between an axon and its target cell and subsequently recruit and organize the presynaptic and postsynaptic protein machinery required for synaptic transmission. A new study by Linhoff and colleagues in this issue of Neuron identifies adhesion proteins of the LRRTM family as novel synaptic organizers
Autismus - Wenn Nervenzellen kontaktscheu sind
No full textErkrankungen aus dem Autismus-Spektrum – autism spectrum disorders oder ASDs – sind häufig auftretende Entwicklungsstörungen des Nerven- systems. Epidemiologische und humangenetische Studien lassen auf eine genetische Prädisposition als wesentliche Ursache von ASDs schließen. In einer Reihe jüngst charakterisierter Fälle monogen erblicher ASDs sind Gene betroffen, deren Proteinprodukt e an der Ausbildung glutamaterger Synapsen zwischen Nervenzellen beteiligt sind. In Mausmodellen mit Deletionen dieser Gene ist die synaptische Signalübertragung fundamen- tal gestört. Offenbar sind also zumindest einige ASD-Formen Synapto- pathien
Altered Complexin expression in psychiatric and neurological disorders: Cause or consequence?
No full textComplexins play a critical role in the control of fast synchronous neurotransmitter release. They operate by binding to trimeric SNARE complexes consisting of the vesicle protein Synaptobrevin and the plasma membrane proteins Syntaxin and SNAP-25, which are key executors of membrane fusion reactions. SNARE complex binding by Complexins is thought to stabilize and clamp the SNARE complex in a highly fusogenic state, thereby providing a pool of readily releasable synaptic vesicles that can be released quickly and synchronously in response to an action potential and the concomitant increase in intra-synaptic Ca2+ levels. Genetic elimination of Complexins from mammalian neurons causes a strong reduction in evoked neurotransmitter release, and altered Complexin expression levels with consequent deficits in synaptic transmission were suggested to contribute to the etiology or pathogenesis of schizophrenia, Huntington's disease, depression, bipolar disorder, Parkinson's disease, Alzheimer's disease, traumatic brain injury, Wernicke's encephalopathy, and fetal alcohol syndrome. In the present review I provide a summary of available data on the role of altered Complexin expression in brain diseases. On aggregate, the available information indicates that altered Complexin expression levels are unlikely to have a causal role in the etiology of the disorders that they have been implicated in, but that they may contribute to the corresponding symptoms
Altered Complexin expression in psychiatric and neurological disorders: Cause or consequence?
No full textComplexins play a critical role in the control of fast synchronous neurotransmitter release. They operate by binding to trimeric SNARE complexes consisting of the vesicle protein Synaptobrevin and the plasma membrane proteins Syntaxin and SNAP-25, which are key executors of membrane fusion reactions. SNARE complex binding by Complexins is thought to stabilize and clamp the SNARE complex in a highly fusogenic state, thereby providing a pool of readily releasable synaptic vesicles that can be released quickly and synchronously in response to an action potential and the concomitant increase in intra-synaptic Ca2+ levels. Genetic elimination of Complexins from mammalian neurons causes a strong reduction in evoked neurotransmitter release, and altered Complexin expression levels with consequent deficits in synaptic transmission were suggested to contribute to the etiology or pathogenesis of schizophrenia, Huntington's disease, depression, bipolar disorder, Parkinson's disease, Alzheimer's disease, traumatic brain injury, Wernicke's encephalopathy, and fetal alcohol syndrome. In the present review I provide a summary of available data on the role of altered Complexin expression in brain diseases. On aggregate, the available information indicates that altered Complexin expression levels are unlikely to have a causal role in the etiology of the disorders that they have been implicated in, but that they may contribute to the corresponding symptoms
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