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Gene Review

REM1  -  RAS (RAD and GEM)-like GTP-binding 1

Homo sapiens

Synonyms: GD:REM, GES, GTP-binding protein REM 1, GTPase-regulating endothelial cell sprouting, REM, ...
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Disease relevance of REM1


Psychiatry related information on REM1

  • Letter: Narcolepsy: REM sleep suppression by L-dopa [6].
  • We propose that the function of dream sleep (more properly rapid-eye movement or REM sleep) is to remove certain undesirable modes of interaction in networks of cells in the cerebral cortex [7].
  • Humans with pharmacological and brain lesion-induced suppression of REM sleep do not show memory deficits, and other human sleep-learning studies have not produced consistent results [8].
  • Spontaneous brain oscillations during states of vigilance are associated with neuronal plasticity due to rhythmic spike bursts and spike trains fired by thalamic and neocortical neurons during low-frequency rhythms that characterize slow-wave sleep and fast rhythms occurring during waking and REM sleep [9].
  • The main clinical features of narcolepsy, excessive daytime sleepiness and symptoms of abnormal REM sleep (cataplexy, sleep paralysis, hypnagogic hallucinations) are currently treated using amphetamine-like compounds or modafinil and antidepressants [10].

High impact information on REM1

  • It has been hypothesized that REM (rapid eye movement) sleep has an important role in memory consolidation [8].
  • Dreaming can be manipulated by dopamine agonists and antagonists with no concomitant change in REM frequency, duration, and density [11].
  • Recent neuropsychological, radiological, and pharmacological findings suggest that the cholinergic brain stem mechanisms that control the REM state can only generate the psychological phenomena of dreaming through the mediation of a second, probably dopaminergic, forebrain mechanism [11].
  • A mounting body of evidence suggests that dreaming and REM sleep are dissociable states, and that dreaming is controlled by forebrain mechanisms [11].
  • We propose that the primary function of REM sleep is to provide periodic endogenous stimulation to the brain which serves to maintain requisite levels of central nervous system (CNS) activity throughout sleep [12].

Chemical compound and disease context of REM1

  • Acetylcholine and the regulation of REM sleep: basic mechanisms and clinical implications for affective illness and narcolepsy [13].
  • In this view the level of extracellular serotonin would be consistent with the pattern of discharge of the DRN serotonergic neurons which show the highest firing rate during W, followed by a decrease in slow wave sleep and by virtual electrical silence during REM sleep [14].
  • With one exception (pimozide), all the drugs that suppressed cataplexy are known to be potent suppressors of REM sleep [15].
  • The biological profile of an anergic episode of bipolar depression did not include a shorter than normal mean REM latency, poor sleep continuity, or abnormally low amounts of stages 3 and 4 sleep, and only three (13%) of 23 patients manifested cortisol nonsuppression [16].
  • Two biological markers--shortened REM latency and nonsuppression on the dexamethasone suppression test--suggested that both patients may have had an underlying affective disorder [17].

Biological context of REM1

  • A new long terminal repeat (LTR) retrotransposon, named REM1, has been identified in the green alga Chlamydomonas reinhardtii [18].
  • Heart rates were counted for a 40-min period following the end of REM1 [19].
  • Furthermore, the rate of REM (rapid eye movement) sleep accumulation , REM latency, bedtime selection, and self-rated alertness assessments were also correlated with the body temperature rhythm [20].
  • We address this issue first on the cellular level, considering how activation of T-type Ca(2+) channels in nonREM sleep may promote either long-term depression or long-term potentiation, as well as how cellular events of REM sleep may influence these processes [21].
  • A cDNA library was constructed from a homozygous B lymphoblastoid cell line (REM) obtained from an individual of a long isolated American Indian tribe, the Warao [22].

Anatomical context of REM1

  • We report that Ges (GTPase regulating endothelial cell sprouting), a human RGK protein expressed in the endothelium, functions as a potent morphogenic switch in endothelial cells (ECs) [23].
  • (2) As well as a role in the mediation of REM sleep, cholinergic PPTg neurons have an important role in the waking state, providing feedback into the thalamus and striatum [24].
  • This observation suggests that CWS (1) can represent a distinct and isolated neuropsychological manifestation of deep occipital lobe damage, and (2) may occur in the absence of detectable REM sleep abnormalities [25].
  • Sequence of a DQ beta clone from the DRw 15-Dw 22 cell line REM [26].
  • REM sleep and amygdala [27].

Associations of REM1 with chemical compounds

  • Analysis of sleep effects of flurazepam hydrochloride on four normal subjects confirmed that this drug substantially suppresses both REM and stage 4 sleep [28].
  • This suggests that during waking serotonin may complement the action of noradrenaline and acetylcholine in promoting cortical responsiveness and participate to the inhibition of REM-sleep effector neurons in the brainstem (inhibitory role on REM sleep) [14].
  • It is a multidomain protein composed of several recognizable sequence motifs in the following order (NH(2) to COOH): pleckstrin homology (PH), coiled-coil, ilimaquinone (IQ), Dbl homology (DH), PH, REM (Ras exchanger motif), PEST/destruction box, Cdc25 [29].
  • In narcoleptics, impaired control of sleep-wake and REM mechanisms is attentuated by methylphenidate [30].
  • However, total times in deeper stages of non-rapid eye movement (non-REM; e.g., delta sleep) and REM sleep were not significantly affected by SCN lesions [31].

Analytical, diagnostic and therapeutic context of REM1


  1. Acetylcholine in mind: a neurotransmitter correlate of consciousness? Perry, E., Walker, M., Grace, J., Perry, R. Trends Neurosci. (1999) [Pubmed]
  2. The effect of oxygen on respiration and sleep in patients with congestive heart failure. Hanly, P.J., Millar, T.W., Steljes, D.G., Baert, R., Frais, M.A., Kryger, M.H. Ann. Intern. Med. (1989) [Pubmed]
  3. Letter: REM sleep and cardiac arrhythmias. Orr, W.C., Shappell, S.D. Circulation (1975) [Pubmed]
  4. Absence of REM and altered NREM sleep in patients with spinocerebellar degeneration and slow saccades. Osorio, I., Daroff, R.B. Ann. Neurol. (1980) [Pubmed]
  5. A polysomnographic and clinical report on sleep-related injury in 100 adult patients. Schenck, C.H., Milner, D.M., Hurwitz, T.D., Bundlie, S.R., Mahowald, M.W. The American journal of psychiatry. (1989) [Pubmed]
  6. Letter: Narcolepsy: REM sleep suppression by L-dopa. Gilbert, J.C., Willer, J.C., Bernheim-Chaltelain, C., Ecoffet, M., Jaillon, P. N. Engl. J. Med. (1976) [Pubmed]
  7. The function of dream sleep. Crick, F., Mitchison, G. Nature (1983) [Pubmed]
  8. The REM sleep-memory consolidation hypothesis. Siegel, J.M. Science (2001) [Pubmed]
  9. Neuronal plasticity in thalamocortical networks during sleep and waking oscillations. Steriade, M., Timofeev, I. Neuron (2003) [Pubmed]
  10. Pharmacological aspects of human and canine narcolepsy. Nishino, S., Mignot, E. Prog. Neurobiol. (1997) [Pubmed]
  11. Dreaming and REM sleep are controlled by different brain mechanisms. Solms, M. The Behavioral and brain sciences. (2000) [Pubmed]
  12. The case against memory consolidation in REM sleep. Vertes, R.P., Eastman, K.E. The Behavioral and brain sciences. (2000) [Pubmed]
  13. Acetylcholine and the regulation of REM sleep: basic mechanisms and clinical implications for affective illness and narcolepsy. Shiromani, P.J., Gillin, J.C., Henriksen, S.J. Annu. Rev. Pharmacol. Toxicol. (1987) [Pubmed]
  14. Serotonin and the sleep/wake cycle: special emphasis on microdialysis studies. Portas, C.M., Bjorvatn, B., Ursin, R. Prog. Neurobiol. (2000) [Pubmed]
  15. Monoaminergic mechanisms and experimental cataplexy. Foutz, A.S., Delashaw, J.B., Guilleminault, C., Dement, W.C. Ann. Neurol. (1981) [Pubmed]
  16. Sleep EEG and DST findings in anergic bipolar depression. Thase, M.E., Himmelhoch, J.M., Mallinger, A.G., Jarrett, D.B., Kupfer, D.J. The American journal of psychiatry. (1989) [Pubmed]
  17. Alprazolam-induced manic episode in two patients with panic disorder. Pecknold, J.C., Fleury, D. The American journal of psychiatry. (1986) [Pubmed]
  18. REM1, a new type of long terminal repeat retrotransposon in Chlamydomonas reinhardtii. Pérez-Alegre, M., Dubus, A., Fernández, E. Mol. Cell. Biol. (2005) [Pubmed]
  19. The cardioacceleratory response to arecoline infusion during sleep in narcoleptic subjects and controls. Baruch, H.L., Kelwala, S., Kapen, S. Sleep. (1987) [Pubmed]
  20. Human sleep: its duration and organization depend on its circadian phase. Czeisler, C.A., Weitzman, E., Moore-Ede, M.C., Zimmerman, J.C., Knauer, R.S. Science (1980) [Pubmed]
  21. Cellular and molecular connections between sleep and synaptic plasticity. Benington, J.H., Frank, M.G. Prog. Neurobiol. (2003) [Pubmed]
  22. Molecular studies of a rare DR2/LD-5a/DQw3 HLA class II haplotype. Multiple genetic mechanisms in the generation of polymorphic HLA class II genes. Liu, C.P., Bach, F.H., Wu, S.K. J. Immunol. (1988) [Pubmed]
  23. Ges, A human GTPase of the Rad/Gem/Kir family, promotes endothelial cell sprouting and cytoskeleton reorganization. Pan, J.Y., Fieles, W.E., White, A.M., Egerton, M.M., Silberstein, D.S. J. Cell Biol. (2000) [Pubmed]
  24. The pedunculopontine tegmental nucleus: where the striatum meets the reticular formation. Inglis, W.L., Winn, P. Prog. Neurobiol. (1995) [Pubmed]
  25. Total dream loss: a distinct neuropsychological dysfunction after bilateral PCA stroke. Bischof, M., Bassetti, C.L. Ann. Neurol. (2004) [Pubmed]
  26. Sequence of a DQ beta clone from the DRw 15-Dw 22 cell line REM. Liu, C.P., Wu, S., Santamaria, P., Segall, M., Bach, F.H. J. Immunol. (1990) [Pubmed]
  27. REM sleep and amygdala. Maquet, P., Franck, G. Mol. Psychiatry (1997) [Pubmed]
  28. Flurazepam effects on sleep EEG. Visual, computer, and cycle analysis. Feinberg, I., Fein, G., Walker, J.M., Price, L.J., Floyd, T.C., March, J.D. Arch. Gen. Psychiatry (1979) [Pubmed]
  29. Calmodulin-independent coordination of Ras and extracellular signal-regulated kinase activation by Ras-GRF2. de Hoog, C.L., Fan, W.T., Goldstein, M.D., Moran, M.F., Koch, C.A. Mol. Cell. Biol. (2000) [Pubmed]
  30. Sleep apnea, narcolepsy, and dreaming: regional cerebral hemodynamics. Meyer, J.S., Sakai, F., Karacan, I., Derman, S., Yamamoto, M. Ann. Neurol. (1980) [Pubmed]
  31. Effect of SCN lesions on sleep in squirrel monkeys: evidence for opponent processes in sleep-wake regulation. Edgar, D.M., Dement, W.C., Fuller, C.A. J. Neurosci. (1993) [Pubmed]
  32. Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2). Greenberg, F., Guzzetta, V., Montes de Oca-Luna, R., Magenis, R.E., Smith, A.C., Richter, S.F., Kondo, I., Dobyns, W.B., Patel, P.I., Lupski, J.R. Am. J. Hum. Genet. (1991) [Pubmed]
  33. Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans. Dijk, D.J., Czeisler, C.A. J. Neurosci. (1995) [Pubmed]
  34. Polysomnographic studies of unmedicated depressed men before and after cognitive behavioral therapy. Thase, M.E., Reynolds, C.F., Frank, E., Jennings, J.R., Nofzinger, E., Fasiczka, A.L., Garamoni, G., Kupfer, D.J. The American journal of psychiatry. (1994) [Pubmed]
  35. Endogenous Excitatory Drive Modulating Respiratory Muscle Activity across Sleep-Wake States. Chan, E., Steenland, H.W., Liu, H., Horner, R.L. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  36. REM sleep abnormalities in a new animal model of endogenous depression. Vogel, G., Neill, D., Kors, D., Hagler, M. Neuroscience and biobehavioral reviews. (1990) [Pubmed]
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