TY  - JOUR
A1  - Beck, Katherina
A1  - Ehmann, Nadine
A1  - Andlauer, Till F. M.
A1  - Ljaschenko, Dmitrij
A1  - Strecker, Katrin
A1  - Fischer, Matthias
A1  - Kittel, Robert J.
A1  - Raabe, Thomas
T1  - Loss of the Coffin-Lowry syndrome-associated gene RSK2 alters ERK activity, synaptic function and axonal transport in Drosophila motoneurons
JF  - Disease Models & Mechanisms
N2  - Plastic changes in synaptic properties are considered as fundamental for adaptive behaviors. Extracellular-signal-regulated kinase (ERK)-mediated signaling has been implicated in regulation of synaptic plasticity. Ribosomal S6 kinase 2 (RSK2) acts as a regulator and downstream effector of ERK. In the brain, RSK2 is predominantly expressed in regions required for learning and memory. Loss-of-function mutations in human RSK2 cause Coffin-Lowry syndrome, which is characterized by severe mental retardation and low IQ scores in affected males. Knockout of RSK2 in mice or the RSK ortholog in Drosophila results in a variety of learning and memory defects. However, overall brain structure in these animals is not affected, leaving open the question of the pathophysiological consequences. Using the fly neuromuscular system as a model for excitatory glutamatergic synapses, we show that removal of RSK function causes distinct defects in motoneurons and at the neuromuscular junction. Based on histochemical and electrophysiological analyses, we conclude that RSK is required for normal synaptic morphology and function. Furthermore, loss of RSK function interferes with ERK signaling at different levels. Elevated ERK activity was evident in the somata of motoneurons, whereas decreased ERK activity was observed in axons and the presynapse. In addition, we uncovered a novel function of RSK in anterograde axonal transport. Our results emphasize the importance of fine-tuning ERK activity in neuronal processes underlying higher brain functions. In this context, RSK acts as a modulator of ERK signaling.
KW  - mrsk2 KO mouse
KW  - S6KII RSK
KW  - transmission
KW  - neuromuscular junction
KW  - synapse
KW  - MAPK signaling
KW  - axonal transport
KW  - motoneuron
KW  - RSK
KW  - Drosophila
KW  - mechanisms
KW  - plasticity
KW  - protein kinase
KW  - signal transduction pathway
KW  - mitochondrial transport
KW  - glutamate receptor
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145185
VL  - 8
ER  - 
TY  - JOUR
A1  - Hohoff, Christa
A1  - Gorji, Ali
A1  - Kaiser, Sylvia
A1  - Willscher, Edith
A1  - Korsching, Eberhard
A1  - Ambrée, Oliver
A1  - Arolt, Volker
A1  - Lesch, Klaus-Peter
A1  - Sachser, Norbert
A1  - Deckert, Jürgen
A1  - Lewejohann, Lars
T1  - Effect of Acute Stressor and Serotonin Transporter Genotype on Amygdala First Wave Transcriptome in Mice
JF  - PLoS ONE
N2  - The most prominent brain region evaluating the significance of external stimuli immediately after their onset is the amygdala. Stimuli evaluated as being stressful actuate a number of physiological processes as an immediate stress response. Variation in the serotonin transporter gene has been associated with increased anxiety- and depression-like behavior, altered stress reactivity and adaptation, and pathophysiology of stress-related disorders. In this study the instant reactions to an acute stressor were measured in a serotonin transporter knockout mouse model. Mice lacking the serotonin transporter were verified to be more anxious than their wild-type conspecifics. Genome-wide gene expression changes in the amygdala were measured after the mice were subjected to control condition or to an acute stressor of one minute exposure to water. The dissection of amygdalae and stabilization of RNA was conducted within nine minutes after the onset of the stressor. This extremely short protocol allowed for analysis of first wave primary response genes, typically induced within five to ten minutes of stimulation, and was performed using Affymetrix GeneChip Mouse Gene 1.0 ST Arrays. RNA profiling revealed a largely new set of differentially expressed primary response genes between the conditions acute stress and control that differed distinctly between wild-type and knockout mice. Consequently, functional categorization and pathway analysis indicated genes related to neuroplasticity and adaptation in wild-types whereas knockouts were characterized by impaired plasticity and genes more related to chronic stress and pathophysiology. Our study therefore disclosed different coping styles dependent on serotonin transporter genotype even directly after the onset of stress and accentuates the role of the serotonergic system in processing stressors and threat in the amygdala. Moreover, several of the first wave primary response genes that we found might provide promising targets for future therapeutic interventions of stress-related disorders also in humans.
KW  - plasticity
KW  - corticotropin releasing factor
KW  - primary response genes
KW  - spatial memory
KW  - knockout mice
KW  - rat brain
KW  - in vivo
KW  - expression
KW  - anxiety
KW  - emotion
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131040
VL  - 8
IS  - 3
ER  -