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PMID:23142642

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Citation

Passantino, R, Cascio, C, Deidda, I, Galizzi, G, Russo, D, Spedale, G and Guarneri, P' (2012) Identifying protein partners of CLN8, an ER-resident protein involved in neuronal ceroid lipofuscinosis. Biochim. Biophys. Acta '

Abstract

Neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of neurodegenerative diseases characterized by cognitive and motor decline, epilepsy, visual loss and by lysosomal autofluorescent inclusions. Two distinct clinical phenotypes, the progressive epilepsy with mental retardation (EPMR) and a late-infantile variant of NCLs (CLN8-vLINCL) are associated with mutations in the CLN8 gene that encodes a transmembrane protein predominantly located to the endoplasmic reticulum (ER). To gain insight into the function of CLN8 protein, we employed the split-ubiquitin membrane-based yeast two-hybrid (MYTH) system, which detects protein-protein interactions in a membrane environment, using the full-length human CLN8 as bait and a human brain cDNA library as prey. We identified several potential protein partners of CLN8 and especially referred to VAPA, c14orf1/hERG28, STX8, GATE16, BNIP3 and BNIP3L proteins that are associated with biologically relevant processes such as synthesis and transport of lipids, vesicular/membrane trafficking, autophagy/mitophagy and apoptosis. Interactions of CLN8 with VAPA and GATE16 were further validated by co-immunoprecipitation and co-localization assays in mammalian cells. Using a new C-terminal-oriented CLN8 antibody, CLN8-VAPA interaction was also confirmed by co-staining in close spatial proximity within different CNS tissues. The results of this study shed light on potential interactome networks of CLN8 and provide a powerful starting point for understanding protein function(s) and molecular aspects of diseases associated with CLN8 deficiency.

Links

PubMed Online version:10.1016/j.bbamcr.2012.10.030

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PDIA6

GO:0006457: protein folding

ECO:0000314:

P

Confirmed with a MYTH screen of human adult brain cDNA library, Table 1 shows the function of PDIA6 in protein folding.

complete
CACAO 5768

HUMAN:VAPA

GO:0006944: cellular membrane fusion

ECO:0000314:

P

Table 1 shows the VAPA protein and its involvement in cellular membrane fusion and lipid metabolism.

complete
CACAO 5759

HUMAN:Q6FII3

GO:0016126: sterol biosynthetic process

ECO:0000314:

P

Table 1 shows how the c14orf1 protein is involved in the synthesis of sterols.

complete
CACAO 5760

HUMAN:STX8

GO:0055037: recycling endosome

ECO:0000314:

C

Confirmed with a MYTH screen of human adult brain cDNA library, Table 1 shows the function of the protien STX8 in endosome trafficking.

complete
CACAO 5762

HUMAN:Q6NVY4

GO:0006914: autophagy

ECO:0000314:

P

Confirmed with a MYTH screen of human adult brain cDNA library, Table 1 shows the protein function of BNIP3 in autophagy and apoptosis.

complete
CACAO 5765

MOUSE:CLN8

GO:0051179: localization

ECO:0000314:

P

Figure 5 shows the co-localization of CLN8 with the GATE16 protein.

complete
CACAO 5776

MOUSE:CLN8

GO:0045184: establishment of protein localization

ECO:0000314:

P

Figure 6. Co-localization of CLN8 and VAPA in the adult mouse CNS tissues.

complete
CACAO 6821


See also

References

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