CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein

Mole, Sara; Michaux, Grégoire; Codlin, Sandra; Wheeler, Ruth; Sharp, J; Cutler, Daniel F.

doi:10.1016/j.yexcr.2004.04.042

Cited by 100 publications

(76 citation statements)

References 29 publications

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“…The monoclonal anti-myc-antibody was a gift from Judith Blanz (ZMNH, Hamburg, Germany), and the monoclonal antibody against protein disulfide isomerase (PDI) and GM130 were purchased from Stressgen Biotechnologies Corp. (Victoria, BC, Canada). The polyclonal anti-CLN6-antibody 1747 was raised in rabbits against a peptide containing amino acids (aa) 1Á15 as described recently (Mole et al 2004). The polyclonal anti-CLN8 antibody was produced by immunizing rabbits with a peptide corresponding to amino acids 268 Á286 of CLN8 as described previously (Lonka et al 2000).…”

Section: Antibodiesmentioning

confidence: 99%

“…Overexpressed CLN3 was found in the late endosomal/lysosomal compartment, at the plasma membrane and in neuronal cells in synaptosomes and endosomes (Järvelä et al 1998, Kyttälä et al 2004) and has been reported to play a role in arginine transport (Kim et al 2003). CLN6 and CLN8 are localized in the endoplasmic reticulum (ER) and CLN8 traffics to the ER-Golgi intermediate compartment (ER-GIC) (Lonka et al 2000, Heine et al 2004, Mole et al 2004. The function and interacting cytosolic and/or luminal proteins of both CLN6 and CLN8 are unknown.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Antibodiesmentioning

confidence: 99%

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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“…The NCLs are inherited in an autosomal recessive manner and six human NCL genes have now been identified (International Batten Disease Consortium, 1995;Gao et al, 2002;Ranta et al, 1999;Savukoski et al, 1998;Sleat et al, 1997;Vesa et al, 1995;Vines et al, 1999;Wheeler et al, 2002). Despite a common cellular phenotype of disturbed lysosomal function, not all of the proteins causing NCL are located in this organelle (Heine et al, 2004;Isosomppi et al, 2002;Järvelä et al, 1999;Järvelä et al, 1998;Lonka et al, 2000;Lonka et al, 2004;Mole et al, 2004;Ranta et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

btn1, theSchizosaccharomyces pombehomologue of the human Batten disease geneCLN3, regulates vacuole homeostasis

Gachet

Codlin

Hyams

et al. 2005

Journal of Cell Science

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“…It is localized in the ER and in neuronal cells it is additionally found along neural extension in subdomains of a tubular ER network. It contains a N-terminal cytoplasmic domain, seven putative transmembrane domains and a C-terminal luminal domain (Heine et al, 2004;Mole et al, 2004). The main storage component in NCL6 cells is the subunit c of the mitochondrial ATP Synthase (Elleder et al., 2006).…”

Section: Wwwintechopencommentioning

confidence: 99%

Myoclonic Epilepsy in Lysosomal Storage Disorders

Dardis¹,

Bembi²

2011

Novel Aspects on Epilepsy

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CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein

Cited by 100 publications

References 29 publications

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

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

btn1, theSchizosaccharomyces pombehomologue of the human Batten disease geneCLN3, regulates vacuole homeostasis

Myoclonic Epilepsy in Lysosomal Storage Disorders

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