NFAT regulates pre-synaptic development and activity-dependent plasticity in Drosophila

Freeman, Amanda; Franciscovich, Amy; Bowers, Mallory E.; Sandstrom, David J.; Sanyal, Subhabrata

doi:10.1016/j.mcn.2010.12.010

Cited by 26 publications

(29 citation statements)

References 60 publications

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“…However, our findings suggest the iav 1 and calcineurin mutant phenotypes studied here are unlikely to be NFAT dependent because NFAT knockouts display an increase in bouton number (Freeman et al, 2011) rather than the decrease observed in the iav 1 and calcineurin mutants. Thus, in the context of NMJ synapse development, calcineurin appears to function via Futsch rather than NFAT.…”

Section: Discussionmentioning

confidence: 55%

A TRPV Channel in Drosophila Motor Neurons Regulates Presynaptic Resting Ca2+ Levels, Synapse Growth, and Synaptic Transmission

Wong

Chen

Lin

et al. 2014

Neuron

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SUMMARY Presynaptic resting Ca2+ influences synaptic vesicle (SV) release probability. Here, we report that a TRPV channel, Inactive (Iav), maintains presynaptic resting [Ca2+] by promoting Ca2+ release from the endoplasmic reticulum in Drosophila motor neurons, and is required for both synapse development and neurotransmission. We find that Iav activates the Ca2+/calmodulin-dependent protein phosphatase, calcineurin, which is essential for presynaptic microtubule stabilization at the neuromuscular junction. Thus, loss of Iav induces destabilization of presynaptic microtubules resulting in diminished synaptic growth. Interestingly, expression of human TRPV1 in Iav-deficient motor neurons rescues these defects. We also show that the absence of Iav causes lower SV release probability and diminished synaptic transmission, whereas Iav overexpression elevates these synaptic parameters. Together, our findings indicate that Iav acts as a key regulator of synaptic development and function by influencing presynaptic resting [Ca2+].

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Section: Discussionmentioning

confidence: 55%

A TRPV Channel in Drosophila Motor Neurons Regulates Presynaptic Resting Ca2+ Levels, Synapse Growth, and Synaptic Transmission

Wong

Chen

Lin

et al. 2014

Neuron

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“…Since the larval neuro-muscular system is simpler and experimentally more accessible than in the adult, we used this model synapse to test our idea. Baseline synaptic transmission was measured at the muscle 6/7 motor synapse in abdominal segment A2 in 1 mM external calcium as reported previously (Freeman et al, 2011; Sen et al, 2011). elav C155 -GAL4 was used to drive expression of full-length Smn or RNAi constructs as described in previous sections.…”

Section: Resultsmentioning

confidence: 99%

Behavioral and electrophysiological outcomes of tissue-specific Smn knockdown in Drosophila melanogaster

Timmerman

Sanyal

2012

Brain Research

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Severe reduction in Survival Motor Neuron 1 (SMN1) protein in humans causes Spinal Muscular Atrophy (SMA), a debilitating childhood disease that leads to progressive impairment of the neuro-muscular system. Although previous studies have attempted to identify the tissue(s) in which SMN1 loss most critically leads to disease, tissue-specific functions for this widely expressed protein still remain unclear. Here, we have leveraged RNA interference methods to manipulate SMN function selectively in Drosophila neurons or muscles followed by behavioral and electrophysiological analysis. High resolution measurement of motor performance shows profound alterations in locomotor patterns following pan-neuronal knockdown of SMN. Further, locomotor phenotypes can be elicited by SMN knockdown in motor neurons, supporting previous demonstrations of motor neuron-specific SMN function in mice. Electrophysiologically, SMN modulation in muscles reveals largely normal synaptic transmission, quantal release and trans-synaptic homeostatic compensation at the larval neuro-muscular junction. Neuronal SMN knockdown does not alter baseline synaptic transmission, the dynamics of synaptic depletion or acute homeostatic compensation. However, chronic glutamate receptor-dependent developmental homeostasis at the neuro-muscular junction is strongly attenuated following reduction of SMN in neurons. Together, these results support a distributed model of SMN function with distinct neuron-specific roles that are likely to be compromised following global loss of SMN in patients. While complementary to, and in broad agreement with, recent mouse studies that suggest a strong necessity for SMN in neurons, our results uncover a hitherto under-appreciated role for SMN in homeostatic regulatory mechanisms at motor synapses.

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“…At the molecular level, NFAT-directed gene transcription regulates the expression of several key proteins critical for activity responses including IP 3 Rs, GluRs, and pro-nociceptive genes in neurons [102–104]. Calcineurin-NFAT signaling is critical for neurotrophin-mediated axonal growth and guidance during vertebrate development [105,106] as well as presynaptic development [107], dendritogenesis [108], and neuronal survival [107–110]. …”

Section: Physiological Roles Of Ca2+ Signaling In Neural Developmentmentioning

confidence: 99%

Regulation of neurogenesis by calcium signaling

2016

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Calcium (Ca2+) signaling has essential roles in the development of the nervous system from neural induction to the proliferation, migration, and differentiation of neural cells. Ca2+ signaling pathways are shaped by interactions among metabotropic signaling cascades, intracellular Ca2+ stores, ion channels, and a multitude of downstream effector proteins that activate specific genetic programs. The temporal and spatial dynamics of Ca2+ signals are widely presumed to control the highly diverse yet specific genetic programs that establish the complex structures of the adult nervous system. Progress in the last two decades has led to significant advances in our understanding of the functional architecture of Ca2+ signaling networks involved in neurogenesis. In this review, we assess the literature on the molecular and functional organization of Ca2+ signaling networks in the developing nervous system and its impact on neural induction, gene expression, proliferation, migration, and differentiation. Particular emphasis is placed on the growing evidence for the involvement of store-operated Ca2+ release-activated Ca2+ (CRAC) channels in these processes.

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NFAT regulates pre-synaptic development and activity-dependent plasticity in Drosophila

Cited by 26 publications

References 60 publications

A TRPV Channel in Drosophila Motor Neurons Regulates Presynaptic Resting Ca2+ Levels, Synapse Growth, and Synaptic Transmission

A TRPV Channel in Drosophila Motor Neurons Regulates Presynaptic Resting Ca2+ Levels, Synapse Growth, and Synaptic Transmission

Behavioral and electrophysiological outcomes of tissue-specific Smn knockdown in Drosophila melanogaster

Regulation of neurogenesis by calcium signaling

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