Sun, 20 Jul 2008 21:39:34 BST CiteULike: lechristophe nmj http://www.citeulike.org/user/lechristophe/tag/nmj CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/lechristophe/article/2713170 <i>Neuron, Vol. 58, No. 2. (24 April 2008), pp. 210-222.</i><br /><br />Summary Synaptic connections are stabilized through transsynaptic adhesion complexes that are anchored in the underlying cytoskeleton. The Drosophila neuromuscular junction (NMJs) serves as a model system to unravel genes required for the structural remodeling of synapses. In a mutagenesis screen for regulators of synaptic stability, we recovered mutations in Drosophila ankyrin 2 (ank2) affecting two giant Ank2 isoforms that are specifically expressed in the nervous system and associate with the presynaptic membrane cytoskeleton. ank2 mutant larvae show severe deficits in the stability of NMJs, resulting in a reduction in overall terminal size, withdrawal of synaptic boutons, and disassembly of presynaptic active zones. In addition, lack of Ank2 leads to disintegration of the synaptic microtubule cytoskeleton. Microtubules and microtubule-associated proteins fail to extend into distant boutons. Interestingly, Ank2 functions downstream of spectrin in the anchorage of synaptic microtubules, providing the cytoskeletal scaffold that is essential for synaptic stability. Drosophila Ankyrin 2 Is Required for Synaptic Stability Iris Koch Heinz Schwarz Dirk Beuchle Bernd Goellner Maria Langegger Hermann Aberle doi:10.1016/j.neuron.2008.03.019 Neuron, Vol. 58, No. 2. (24 April 2008), pp. 210-222. 2008-04-24T14:24:05-00:00 2008 Neuron 58 2 210 222 ankyrin drosophila nmj spectrin http://www.citeulike.org/user/lechristophe/article/2713166 <i>Neuron, Vol. 58, No. 2. (24 April 2008), pp. 195-209.</i><br /><br />Summary In a forward genetic screen for mutations that destabilize the neuromuscular junction, we identified a novel long isoform of Drosophila ankyrin2 (ank2-L). We demonstrate that loss of presynaptic Ank2-L not only causes synapse disassembly and retraction but also disrupts neuronal excitability and NMJ morphology. We provide genetic evidence that ank2-L is necessary to generate the membrane constrictions that normally separate individual synaptic boutons and is necessary to achieve the normal spacing of subsynaptic protein domains, including the normal organization of synaptic cell adhesion molecules. Mechanistically, synapse organization is correlated with a lattice-like organization of Ank2-L, visualized using extended high-resolution structured-illumination microscopy. The stabilizing functions of Ank2-L can be mapped to the extended C-terminal domain that we demonstrate can directly bind and organize synaptic microtubules. We propose that a presynaptic Ank2-L lattice links synaptic membrane proteins and spectrin to the underlying microtubule cytoskeleton to organize and stabilize the presynaptic terminal. A Presynaptic Giant Ankyrin Stabilizes the NMJ through Regulation of Presynaptic Microtubules and Transsynaptic Cell Adhesion Jan Pielage Ling Cheng Richard Fetter Pete Carlton John Sedat Graeme Davis doi:10.1016/j.neuron.2008.02.017 Neuron, Vol. 58, No. 2. (24 April 2008), pp. 195-209. 2008-04-24T14:22:25-00:00 2008 Neuron 58 2 195 209 ankyrin drosophila nmj spectrin http://www.citeulike.org/user/lechristophe/article/744624 <i>Genes Dev., Vol. 20, No. 13. (1 July 2006), pp. 1800-1816.</i><br /><br />The release of Agrin by motoneurons activates the muscle-specific receptor tyrosine kinase (MuSK) as the main organizer of subsynaptic specializations at the neuromuscular junction. MuSK downstream signaling is largely undefined. Here we show that protein kinase CK2 interacts and colocalizes with MuSK at post-synaptic specializations. We observed CK2-mediated phosphorylation of serine residues within the kinase insert (KI) of MuSK. Inhibition or knockdown of CK2, or exchange of phosphorylatable serines by alanines within the KI of MuSK, impaired acetylcholine receptor (AChR) clustering, whereas their substitution by residues that imitate constitutive phosphorylation led to aggregation of AChRs even in the presence of CK2 inhibitors. Impairment of AChR cluster formation after replacement of MuSK KI with KIs of other receptor tyrosine kinases correlates with potential CK2-dependent serine phosphorylation within KIs. MuSK activity was unchanged but AChR stability decreased in the presence of CK2 inhibitors. Muscle-specific CK2[beta] knockout mice develop a myasthenic phenotype due to impaired muscle endplate structure and function. This is the first description of a regulatory cross-talk between MuSK and CK2 and of a role for the KI of the receptor tyrosine kinase MuSK for the development of subsynaptic specializations. 10.1101/gad.375206 Casein kinase 2-dependent serine phosphorylation of MuSK regulates acetylcholine receptor aggregation at the neuromuscular junction Tatiana Cheusova Muhammad Khan Steffen Schubert Anne-Claude Gavin Thierry Buchou Germaine Jacob Heinrich Sticht Jorge Allende Brigitte Boldyreff Hans Brenner Said Hashemolhosseini doi:10.1101/gad.375206 Genes Dev., Vol. 20, No. 13. (1 July 2006), pp. 1800-1816. 2006-07-07T02:37:46-00:00 2006 Genes Dev. 20 13 1800 1816 caseine_kinase nmj phosphorylation