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  - Planes, Maria D.
A1  - Niñoles, Regina
A1  - Rubio, Lourdes
A1  - Bissoli, Gaetano
A1  - Bueso, Eduardo
A1  - García-Sánchez, María J.
A1  - Alejandro, Santiago
A1  - Gonzalez-Guzmán, Miguel
A1  - Hedrich, Rainer
A1  - Rodriguez, Pedro L.
A1  - Fernández, José A.
A1  - Serrano, Ramón
T1  - A mechanism of growth inhibition by abscisic acid in germinating seeds of Arabidopsis thaliana based on inhibition of plasma membrane \(H^+\)-ATPase and decreased cytosolic pH, \(K^+\), and anions
JF  - Journal of Experimental Botany
N2  - The stress hormone abscisic acid (ABA) induces expression of defence genes in many organs, modulates ion homeostasis and metabolism in guard cells, and inhibits germination and seedling growth. Concerning the latter effect, several mutants of Arabidopsis thaliana with improved capability for \(H^+\) efflux (wat1-1D, overexpression of AKT1 and ost2-1D) are less sensitive to inhibition by ABA than the wild type. This suggested that ABA could inhibit \(H^+\) efflux (\(H^+\)-ATPase) and induce cytosolic acidification as a mechanism of growth inhibition. Measurements to test this hypothesis could not be done in germinating seeds and we used roots as the most convenient system. ABA inhibited the root plasma-membrane H+-ATPase measured in vitro (ATP hydrolysis by isolated vesicles) and in vivo (\(H^+\) efflux from seedling roots). This inhibition involved the core ABA signalling elements: PYR/PYL/RCAR ABA receptors, ABA-inhibited protein phosphatases (HAB1), and ABA-activated protein kinases (SnRK2.2 and SnRK2.3). Electrophysiological measurements in root epidermal cells indicated that ABA, acting through the PYR/PYL/RCAR receptors, induced membrane hyperpolarization (due to \(K^+\) efflux through the GORK channel) and cytosolic acidification. This acidification was not observed in the wat1-1D mutant. The mechanism of inhibition of the \(H^+\)-ATPase by ABA and its effects on cytosolic pH and membrane potential in roots were different from those in guard cells. ABA did not affect the in vivo phosphorylation level of the known activating site (penultimate threonine) of (\(H^+\)-ATPase in roots, and SnRK2.2 phosphorylated in vitro the C-terminal regulatory domain of (\(H^+\)-ATPase while the guard-cell kinase SnRK2.6/OST1 did not.
KW  - ABA receptors
KW  - cytosolic pH
KW  - ion channels
KW  - microelectrodes
KW  - protein kinase
KW  - proton efflux
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121221
VL  - 66
IS  - 3
ER  -