Alternative titles; symbols
HGNC Approved Gene Symbol: CALCOCO2
Cytogenetic location: 17q21.32 Genomic coordinates (GRCh38): 17:48,831,035-48,865,245 (from NCBI)
ND10 bodies are nuclear domains appearing immunohistochemically as 10 dots per nucleus. The dots do not colocalize with kinetochores, centromeres, mRNA processing sites, or chromosomes. On the basis of their resistance to nuclease digestion and salt extraction, they are believed to be associated with the nuclear matrix. Viral infection removes ND10-associated proteins from the nucleus (summary by Korioth et al., 1995). By immunoscreening a directional MG63 cDNA library and using 5-prime RACE, Korioth et al. (1995) obtained a cDNA encoding a 446-amino acid protein, which they termed NDP52 for nuclear dot protein 52 kD. NDP52 contains a central coiled coil with an integrated leucine zipper, multiple phosphorylation sites, and a LIM-like domain at the cysteine-rich C terminus. Northern blot analysis revealed ubiquitous expression of a 2.5-kb transcript, with highest levels in skeletal muscle and lowest levels in brain. Korioth et al. (1995) also detected the transcript in MG63, SK-ES-1, and HeLa cell lines but not in primary skin fibroblasts. By confocal immunofluorescence microscopy, the authors showed that NDP52 colocalizes with PML (102578), which is known to overlap with SP100 (604585) and NDP55; thus, all are part of ND10. NDP52 also appears to colocalize with the splicing factor SC35 (Spector, 1993). Herpes simplex virus-1 infection removed NDP52 and PML from the nucleus, although traces of the former remained in the splicing factor regions. Adenovirus-5 infection, on the other hand, segregated the ND10-associated proteins into 2 to 3 micrometer tracks. Treatment with IFNB (see 147640) or IFNG (147570) resulted in an increase in size and number of NDP52 dots and partial relocation of NDP52 to the cytoplasm.
Thurston et al. (2012) demonstrated in human cells that galectin-8 (LGALS8; 606099), a cytosolic lectin, is a danger receptor that restricts Salmonella proliferation. Galectin-8 monitors endosomal and lysosomal integrity and detects bacterial invasion by binding host glycans exposed on damaged Salmonella-containing vacuoles. By recruiting NDP52, galectin-8 activates antibacterial autophagy. Galectin-8-dependent recruitment of NDP52 to Salmonella-containing vesicles is transient and followed by ubiquitin-dependent NDP52 recruitment. Because galectin-8 also detects sterile damage to endosomes or lysosomes, as well as invasion by Listeria or Shigella, Thurston et al. (2012) suggested that galectin-8 serves as a versatile receptor for vesicle-damaging pathogens. The results of Thurston et al. (2012) also illustrated how cells deploy the danger receptor galectin-8 to combat infection by monitoring endosomal and lysosomal integrity on the basis of the specific lack of complex carbohydrates in the cytosol.
Lazarou et al. (2015) used genome editing to knock out 5 autophagy receptors in HeLa cells and demonstrated that 2 receptors previously linked to xenophagy, NDP52 and optineurin (602432), are the primary receptors for PINK1 (608309)- and parkin (602544)-mediated mitophagy. PINK1 recruits NDP52 and optineurin but not p62 (SQSTM1; 601530) to mitochondria to activate mitophagy directly, independently of parkin. Once recruited to mitochondria, NDP52 and optineurin recruit the autophagy factors ULK1 (603168), DFCP1 (ZNFN2A1; 605471), and WIPI1 (609224) to focal spots proximal to mitochondria, revealing a function for these autophagy receptors upstream of LC3 (MAP1LC3A; 601242). Lazarou et al. (2015) concluded that their observations support a model in which PINK1-generated phosph-ubiquitin serves as the autophagy signal on mitochondria, and parkin then acts to amplify this signal.
Korioth, F., Gieffers, C., Maul, G. G., Frey, J. Molecular characterization of NDP52, a novel protein of the nuclear domain 10, which is redistributed upon virus infection and interferon treatment. J. Cell Biol. 130: 1-13, 1995. [PubMed: 7540613] [Full Text: https://doi.org/10.1083/jcb.130.1.1]
Lazarou, M., Sliter, D. A., Kane, L. A., Sarraf, S. A., Wang, C., Burman, J. L., Sideris, D. P., Fogel, A. I., Youle, R. J. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524: 309-314, 2015. [PubMed: 26266977] [Full Text: https://doi.org/10.1038/nature14893]
Spector, D. L. Macromolecular domains within the cell nucleus. Annu. Rev. Cell Biol. 9: 265-315, 1993. [PubMed: 8280462] [Full Text: https://doi.org/10.1146/annurev.cb.09.110193.001405]
Thurston, T. L. M., Wandel, M. P., von Muhlinen, N., Foeglein, A., Randow, F. Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion. Nature 482: 414-418, 2012. [PubMed: 22246324] [Full Text: https://doi.org/10.1038/nature10744]