Neuronal Ceroid-Lipofuscinoses

Tyynelä, Jaana

doi:10.1007/0-387-28957-7_8

Cited by 7 publications

(5 citation statements)

References 120 publications

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“…Subunit c of ATP synthase is a component of ceroid lipofuscin that accumulates in neurons of patients suffering from a subclass of ceroid lipofuscinoses, a group of fatal neurodegenerative diseases. 83,84 In humans, this disease subclass is caused by mutations in CLN genes (numbers 2, 3, 4, 5, 6, 7 and 8), encoding either the lysosomal enzyme tripeptidyl peptidase I, or a group of novel lysosomal membrane proteins. The rest of neuronal ceroid lipofucsinoses are caused by mutations in the CLN1 gene, encoding the enzyme palmitoyl protein thioesterase.…”

Section: Regulation Of the Fusion Eventsmentioning

confidence: 99%

Maturation of Autophagic Vacuoles in Mammalian Cells

2005

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Section: Regulation Of the Fusion Eventsmentioning

confidence: 99%

Maturation of Autophagic Vacuoles in Mammalian Cells

2005

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“…Sleep questionnaires were obtained for the patients under 20 years of age (mean age 14 years). Questionnaire data were not available for the four older patients in an advanced stage of the disease (age range [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]…”

Section: Polysomnographymentioning

confidence: 99%

Sleep and Its Disturbance in a Variant Form of Late Infantile Neuronal Ceroid Lipofuscinosis (CLNS)

Kirveskari

Partinen²,

Santavuori

2001

J Child Neurol

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To examine the nature of sleep disturbance in patients with a variant form of late infantile neuronal ceroid lipofuscinosis (CLN5), we studied 12 patients (age range 7-32 years). We used a sleep questionnaire to assess sleep and its disturbances quantitatively. To identify the periodicity in the diurnal rest-activity rhythms, the motor activity level was recorded by activity monitors continuously for a 1-week period with concomitant sleep logs. In addition, whole-night polysomnographic recordings were performed. The patients under 20 years of age had an excess of nocturnal sleep (the mean of the usual duration of nighttime sleep was 10.0 hours) and frequent daytime naps. Frequent shifts of the longest sleep period into the daytime hours and fragmented diurnal rest-activity patterns with no distinct rhythm occurred in the older patients. The progressive disease may damage the internal circadian timing system and also impair the ability of patients with variant late infantile neuronal ceroid lipofuscinosis to use external time cues for synchronization of their sleep and environmental time.

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“…They share common clinical features including visual failure leading to blindness, seizures, myoclonic epilepsies, and progressive mental and motor deterioration (Santavuori et al 2001). NCLs are characterized by massive lysosomal storage of autofluorescent ceroid and lipofuscin as well as aggregated proteins such as subunit c of the mitochondrial ATP synthase or sphingolipid activator proteins (Tyynelä 2005). Currently, seven human NCL genes have been identified.…”

Section: Introductionmentioning

confidence: 99%

Topology and endoplasmic reticulum retention signals of the lysosomal storage disease-related membrane protein CLN6

Heine

Quitsch

Storch

et al. 2007

Molecular Membrane Biology

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CLN6 is a polytopic membrane protein of unknown function resident in the endoplasmic reticulum (ER). Mutant CLN6 causes the lysosomal storage disorder neuronal ceroid lipofuscinosis. Defining the topology of CLN6, and the structural domains and motifs required for interaction with cytosolic and luminal proteins may allow insights into its function. In this study we analysed the topology, ER retention and oligomerization of CLN6. We demonstrated, by differential membrane permeabilization of transfected BHK cells using specific detergents and two distinct antibodies, that CLN6 contains an N-terminal cytoplasmic domain, seven transmembrane domains, and a luminal C terminus. Mutational analyses and confocal immunofluorescence microscopy showed that changes of potential ER localization signals in the N- or C-terminal domain (a triple arginine cluster, and a dileucine motif) did not alter the subcellular localization of CLN6. The deletion of a dilysine motif impaired partially the ER localization of CLN6. Furthermore, expression analyses of fusion and deletion constructs in non-neuronal and neuronal cells suggested that two portions of CLN6 contributed to its retention within the ER. We showed that the N-terminal domain was necessary but not sufficient for ER retention of CLN6 and that deletion of transmembrane domains 6 and 7 was accompanied with the loss of ER localization and, in some instances, trafficking to the cisGolgi. From these data we concluded that CLN6 maintains its ER localization by expressing retention signals present in both the N-terminal cytosolic domain and in the carboxy-proximal transmembrane domains 6 and 7. Additionally, the ability of CLN6 to homodimerize may also prevent exit from the ER via an interaction with membrane-associated factors.

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Neuronal Ceroid-Lipofuscinoses

Cited by 7 publications

References 120 publications

Maturation of Autophagic Vacuoles in Mammalian Cells

Maturation of Autophagic Vacuoles in Mammalian Cells

Sleep and Its Disturbance in a Variant Form of Late Infantile Neuronal Ceroid Lipofuscinosis (CLNS)

Topology and endoplasmic reticulum retention signals of the lysosomal storage disease-related membrane protein CLN6

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