The RhoGAPcrossveinless-cInteracts withDystrophinand Is Required for Synaptic Homeostasis at theDrosophilaNeuromuscular Junction

Pilgram, Gonneke S. K.; Potikanond, Saranyapin; Plas, Mariska C. van der; Fradkin, Lee G.; Noordermeer, Jasprina N.

doi:10.1523/jneurosci.4732-10.2011

Cited by 19 publications

(20 citation statements)

References 60 publications

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“…Examples include mutations in the nuclear import gene importin13 (85), in the genes encoding components of the Dystrophin/Dystroglycan protein complex (86), and in genes encoding Rho-GAP/Cdc42-mediated signaling (87); see Reference 13 for a more extensive review of these signaling systems. However, until these signaling systems are tested in the background of a homeostatic challenge, it is not possible to ascribe an activity that is directly related to homeostatic plasticity.…”

Section: Postsynaptic Mechanisms: Scaffolds Sensors and Signalingmentioning

confidence: 99%

“…(a) (Left) Cartoon of a synapse with a local calcium domain (red ). Shown are postsynaptic genes implicated in the control of baseline presynaptic release, including those encoding Dystrophin, Distrobrevin(86,110), and Importin13(85). (Right) Following philanthotoxin (PhTx) or glutamate receptor (GluR) perturbation, there is an increase in presynaptic calcium influx (red; 57) and an increase in the readily releasable pool (RRP) of vesicles(51,52).…”

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confidence: 99%

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Homeostatic Control of Presynaptic Neurotransmitter Release

Davis

Müller

2015

Annu. Rev. Physiol.

235

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It is well established that the active properties of nerve and muscle cells are stabilized by homeostatic signaling systems. In organisms ranging from Drosophila to humans, neurons restore baseline function in the continued presence of destabilizing perturbations by rebalancing ion channel expression, modifying neurotransmitter receptor surface expression and trafficking, and modulating neurotransmitter release. This review focuses on the homeostatic modulation of presynaptic neurotransmitter release, termed presynaptic homeostasis. First, we highlight criteria that can be used to define a process as being under homeostatic control. Next, we review the remarkable conservation of presynaptic homeostasis at the Drosophila, mouse, and human neuromuscular junctions and emerging parallels at synaptic connections in the mammalian central nervous system. We then highlight recent progress identifying cellular and molecular mechanisms. We conclude by reviewing emerging parallels between the mechanisms of homeostatic signaling and genetic links to neurological disease.

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Section: Postsynaptic Mechanisms: Scaffolds Sensors and Signalingmentioning

confidence: 99%

mentioning

confidence: 99%

Homeostatic Control of Presynaptic Neurotransmitter Release

Davis

Müller

2015

Annu. Rev. Physiol.

235

250

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“…A genetic screen found that cv-c loss-of-function mutations interact genetically with dystrophin mutations in Drosophila wing cross vein formation (Pilgram et al, 2011). Examination of the dystrophin / cv-c genetic relationship at the NMJ showed that postsynaptic loss of cv-c phenocopies dystrophin loss (normal quantal size, and significantly increased quantal content) (Pilgram et al, 2011).…”

Section: Postsynaptic Molecules Regulating Retrograde Increases Inmentioning

confidence: 99%

“…Examination of the dystrophin / cv-c genetic relationship at the NMJ showed that postsynaptic loss of cv-c phenocopies dystrophin loss (normal quantal size, and significantly increased quantal content) (Pilgram et al, 2011). Dystrophin appears to act downstream of Cv-c in the muscle.…”

Section: Postsynaptic Molecules Regulating Retrograde Increases Inmentioning

confidence: 99%

Homeostatic plasticity at the Drosophila neuromuscular junction

2014

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In biology, homeostasis refers to how cells maintain appropriate levels of activity. This concept underlies a balancing act in the nervous system. Synapses require flexibility (i.e. plasticity) to adjust to environmental challenges. Yet there must also exist regulatory mechanisms that constrain activity within appropriate physiological ranges. An abundance of evidence suggests that homeostatic regulation is critical in this regard. In recent years, important progress has been made towards identifying molecules and signaling processes required for homeostatic forms of neuroplasticity. The Drosophila melanogaster third instar larval neuromuscular junction (NMJ) has been an important experimental system in this effort. Drosophila neuroscientists combine genetics, pharmacology, electrophysiology, imaging, and a variety of molecular techniques to understand how homeostatic signaling mechanisms take shape at the synapse. At the NMJ, homeostatic signaling mechanisms couple retrograde (muscle-to-nerve) signaling with changes in presynaptic calcium influx, changes in the dynamics of the readily releasable vesicle pool, and ultimately, changes in presynaptic neurotransmitter release. Roles in these processes have been demonstrated for several molecules and signaling systems discussed here. This review focuses primarily on electrophysiological studies or data. In particular, attention is devoted to understanding what happens when NMJ function is challenged (usually through glutamate receptor inhibition) and the resulting homeostatic responses. A significant area of study not covered in this review, for the sake of simplicity, is the homeostatic control of synapse growth, which naturally, could also impinge upon synapse function in myriad ways.

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“…The identification of mammalian Dys as a target for phosphorylation by CaMKII is further suggestive, and it is tempting to speculate that Dys mediates negative feedback upon phosphorylation by CaMKII. NMJ localization of Dys depends on the transmembrane protein dystroglycan (Bogdanik et al 2009), and a genetic modifier screen led to the finding that the RhoGAP crossveinless-c and its target Cdc42 act in concert with Dys (Pilgram et al 2011).…”

Section: Gluriia-dependent Synapse Formation and Plasticitymentioning

confidence: 99%

Glutamate Receptors in Synaptic Assembly and Plasticity: Case Studies on Fly NMJs

Thomas

Sigrist

2012

Synaptic Plasticity

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The molecular and cellular mechanisms that control the composition and functionality of ionotropic glutamate receptors may be considered as most important "set screws" for adjusting excitatory transmission in the course of developmental and experience-dependent changes within neural networks. The Drosophila larval neuromuscular junction has emerged as one important invertebrate model system to study the formation, maintenance, and plasticity-related remodeling of glutamatergic synapses in vivo. By exploiting the unique genetic accessibility of this organism combined with diverse tools for manipulation and analysis including electrophysiology and state of the art imaging, considerable progress has been made to characterize the role of glutamate receptors during the orchestration of junctional development, synaptic activity, and synaptogenesis. Following an introduction to basic features of this model system, we will mainly focus on conceptually important findings such as the selective impact of glutamate receptor subtypes on the formation of new synapses, the coordination of presynaptic maturation and receptor subtype composition, the role of nonvesicularly released glutamate on the synaptic localization of receptors, or the homeostatic feedback of receptor functionality on presynaptic transmitter release.

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The RhoGAPcrossveinless-cInteracts withDystrophinand Is Required for Synaptic Homeostasis at theDrosophilaNeuromuscular Junction

Abstract: Duchenne muscular dystrophy is caused by mutations in the

Cited by 19 publications

References 60 publications

Homeostatic Control of Presynaptic Neurotransmitter Release

Homeostatic Control of Presynaptic Neurotransmitter Release

Homeostatic plasticity at the Drosophila neuromuscular junction

Glutamate Receptors in Synaptic Assembly and Plasticity: Case Studies on Fly NMJs

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