scholarly journals A genetic screen identifies dreammist as a regulator of sleep

2020 ◽  
Author(s):  
Ida L. Barlow ◽  
Eirinn Mackay ◽  
Emily Wheater ◽  
Aimee Goel ◽  
Sumi Lim ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Movement Disorders ◽  
Transmembrane Protein ◽  
Molecular Genetic ◽  
Genetic Screen ◽  
Night Time ◽  
Single Pass ◽  
Larval Zebrafish ◽  
Universal Feature ◽  
Viral Insertion

AbstractSleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel mutant, dreammist (dmist), with altered sleep-wake dynamics. CRISPR/Cas9-mediated disruption of dmist also led to behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na+,K+-ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na+,K+-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. As intracellular Na+ concentration is disrupted in dmist mutant brains after high neuronal activity similarly to atp1a3a mutants, but is also elevated specifically at night, we propose that sleep-wake stability is modulated by Dmist-dependent changes to Na+ pump function during sleep homeostatic challenge and at specific times of the day-night cycle.

scholarly journals Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e43058 ◽  
Author(s):  
Chiaki Maruta ◽  
Yuhki Saito ◽  
Saori Hata ◽  
Naoya Gotoh ◽  
Toshiharu Suzuki ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Single Pass

scholarly journals The Spectrum of PRRT2-Associated Disorders: Update on Clinical Features and Pathophysiology

2021 ◽  
Vol 12 ◽  
Author(s):  
Annamaria Landolfi ◽  
Paolo Barone ◽  
Roberto Erro
Keyword(s):  
Movement Disorders ◽  
Neurodevelopmental Disorders ◽  
Transmembrane Protein ◽  
Brain Disorders ◽  
Hemiplegic Migraine ◽  
Causative Gene ◽  
Paroxysmal Kinesigenic Dyskinesia ◽  
Infantile Epilepsy ◽  
Biallelic Mutations

Mutations in the PRRT2 (proline-rich transmembrane protein 2) gene have been identified as the main cause of an expanding spectrum of disorders, including paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy, which places this gene at the border between epilepsy and movement disorders. The clinical spectrum has largely expanded to include episodic ataxia, hemiplegic migraine, and complex neurodevelopmental disorders in cases with biallelic mutations. Prior to the discovery of PRRT2 as the causative gene for this spectrum of disorders, the sensitivity of paroxysmal kinesigenic dyskinesia to anticonvulsant drugs regulating ion channel function as well as the co-occurrence of epilepsy in some patients or families fostered the hypothesis this could represent a channelopathy. However, recent evidence implicates PRRT2 in synapse functioning, which disproves the “channel hypothesis” (although PRRT2 modulates ion channels at the presynaptic level), and justifies the classification of these conditions as synaptopathies, an emerging rubric of brain disorders. This review aims to provide an update of the clinical and pathophysiologic features of PRRT2-associated disorders.

scholarly journals Molecular genetic approaches to the targeted suppression of neuronal activity

2001 ◽  
Vol 11 (24) ◽  
pp. R1041-R1053 ◽  
Author(s):  
Benjamin White ◽  
Thomas Osterwalder ◽  
Haig Keshishian
Keyword(s):  
Neuronal Activity ◽  
Molecular Genetic

scholarly journals Imaging Neuronal Activity in the Optic Tectum of Late Stage Larval Zebrafish

2018 ◽  
Vol 6 (1) ◽  
pp. 6 ◽  
Author(s):  
Katharina Bergmann ◽  
Paola Meza Santoscoy ◽  
Konstantinos Lygdas ◽  
Yulia Nikolaeva ◽  
Ryan MacDonald ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Optic Tectum ◽  
Late Stage ◽  
Larval Zebrafish

scholarly journals The neuropeptide Galanin is required for homeostatic rebound sleep following increased neuronal activity

2018 ◽  
Author(s):  
Sabine Reichert ◽  
Oriol Pavón Arocas ◽  
Jason Rihel
Keyword(s):  
Neuronal Activity ◽  
Sleep Time ◽  
Drug Induced ◽  
Extracellular Signal Regulated Kinase ◽  
Larval Zebrafish ◽  
Sleep Homeostasis ◽  
Extracellular Signal ◽  
Sleep Homeostat ◽  
Activity Marker ◽  
Molecular Signals

AbstractSleep pressure homeostatically increases during wake and dissipates during sleep, but the molecular signals and neuronal substrates that measure homeostatic sleep pressure remain poorly understood. We present a pharmacological assay in larval zebrafish that generates acute, short-term increases in wakefulness followed by sustained rebound sleep after washout. The intensity of global neuronal activity during drug-induced wakefulness predicted the amount of subsequent rebound sleep. Whole brain mapping with the neuronal activity marker phosphorylated extracellular signal–regulated kinase (pERK) identified preoptic Galanin-expressing neurons as selectively active during rebound sleep, and the relative induction of galanin transcripts was predictive of total rebound sleep time. Galanin is required for sleep homeostasis, as galanin mutants almost completely lacked rebound sleep following both pharmacologically induced neuronal activity and physical sleep deprivation. These results suggest that Galanin plays a key role in responding to sleep pressure signals derived from neuronal activity and functions as an output arm of the vertebrate sleep homeostat. (word count: 158).

scholarly journals A novel member of the rho family of small GTP-binding proteins is specifically required for cytokinesis.

1996 ◽  
Vol 133 (6) ◽  
pp. 1321-1329 ◽  
Author(s):  
D A Larochelle ◽  
K K Vithalani ◽  
A De Lozanne
Keyword(s):  
Binding Proteins ◽  
Molecular Genetic ◽  
Genetic Screen ◽  
Phenotypic Characterization ◽  
Essential Requirement ◽  
Gtp Binding Proteins ◽  
Gtp Binding ◽  
Subcellular Processes ◽  
Rho Family

Several members of the rho/rac family of small GTP-binding proteins are known to regulate the distribution of the actin cytoskeleton in various subcellular processes. We describe here a novel rac protein, racE, which is specifically required for cytokinesis, an actomyosin-mediated process. The racE gene was isolated in a molecular genetic screen devised to isolate genes required for cytokinesis in Dictyostelium. Phenotypic characterization of racE mutants revealed that racE is not essential for any other cell motility event, including phagocytosis, chemotaxis, capping, or development. Our data provide the first genetic evidence for the essential requirement of a rho-like protein, specifically in cytokinesis, and suggest a role for these proteins in coordinating cytokinesis with the mitotic events of the cell cycle.

scholarly journals Tardive Dyskinesia, Oral Parafunction, and Implant-Supported Rehabilitation

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
S. Lumetti ◽  
G. Ghiacci ◽  
G. M. Macaluso ◽  
M. Amore ◽  
C. Galli ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Movement Disorders ◽  
Ad Hoc ◽  
Mutual Influence ◽  
Pharmacological Intervention ◽  
Edentulous Patient ◽  
Night Time ◽  
Drug Induced ◽  
Splint Therapy ◽  
Titanium Structure

Oral movement disorders may lead to prosthesis and implant failure due to excessive loading. We report on an edentulous patient suffering from drug-induced tardive dyskinesia (TD) and oral parafunction (OP) rehabilitated with implant-supported screw-retained prostheses. The frequency and intensity of the movements were high, and no pharmacological intervention was possible. Moreover, the patient refused night-time splint therapy. A series of implant and prosthetic failures were experienced. Implant failures were all in the maxilla and stopped when a rigid titanium structure was placed to connect implants. Ad hoc designed studies are desirable to elucidate the mutual influence between oral movement disorders and implant-supported rehabilitation.

A single conserved proline residue determines the membrane topology of stomatin

2009 ◽  
Vol 418 (3) ◽  
pp. 587-594 ◽  
Author(s):  
Ivan Kadurin ◽  
Stephan Huber ◽  
Stefan Gründer
Keyword(s):  
Ion Channels ◽  
Transmembrane Protein ◽  
Cell Types ◽  
Membrane Topology ◽  
Hairpin Loop ◽  
Hydrophobic Domain ◽  
Proline Residue ◽  
Single Pass ◽  
Loop Topology ◽  
Related Proteins

Stomatin is an integral membrane protein which is widely expressed in many cell types. It is accepted that stomatin has a unique hairpin-loop topology: it is anchored to the membrane with an N-terminal hydrophobic domain and the N- and C-termini are cytoplasmically localized. Stomatin is a prototype for a family of related proteins, containing among others MEC-2 (mechanosensory protein 2) from Caenorhabditis elegans, SLP (stomatin-like protein)-3 and podocin, all of which interact with ion channels to regulate their activity. Members of the stomatin family partly localize in DRMs (detergent-resistant membrane domains) enriched in cholesterol and sphingolipids. It has been proposed that a highly conserved proline residue in the middle of the hydrophobic domain directly binds cholesterol and that cholesterol binding is necessary for the regulation of ion channels. In the present study we show that a small part of the stomatin pool exists as a single-pass transmembrane protein rather than a hairpin-loop protein. The highly conserved proline residue is crucial for adopting the hairpin-loop topology: substitution of this proline residue by serine transfers the whole stomatin pool to the single-pass transmembrane form, which no longer localizes to DRMs. These results suggest that formation of the hairpin loop is inefficient and that the conserved proline residue is indispensable for formation of the hairpin loop. The single-pass transmembrane form exists also for SLP-3 and it should be considered that it mediates part of the physiological functions of stomatin and related proteins.

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