Nucleoporin 210kDa
Nuclear pore glycoprotein-210 (gp210) is an essential trafficking regulator in the eukaryotic nuclear pore complex. Gp-210 anchors the pore complex to the nuclear membrane.[5] and protein tagging reveals its primarily located on the luminal side of double layer membrane at the pore. A single polypeptide motif of gp210 is responsible for sorting to nuclear membrane,[6] and indicate the carboxyl tail of the protein is oriented toward the cytoplasmic side of the membrane.
Disassembly and Assembly
[edit]During eukaryotic mitosis the nuclear envelope disintegrates into vesicles dispersing nuclear lamina proteins and nuclear pore complexes. Nup210 is specifically phosphorylated on the C-terminal (cytoplasmic) domain in mitosis at Ser1880[7] and is dispersed throughout the endoplasmic reticulum during mitosis as homodimers.[8] Nuclear lamins begin to reassemble around chromosomes at the end of mitosis.[9] Nup210 lags the reassembly process relative to other Nups.[10] and while much of the assembly process can occur without it, the final assembly and dilation of the complexes require Nup210.[11] The replacement of serine at position 1880 with a phosphorylated 'looking' glutamate results in Nup210 complexes that fail to reassemble indicating that dephosphorylation of Nup210 within the final phases of proper assembly is required.[12]
Pathology
[edit]Recognized by anti-nuclear antibodies found in primary biliary cirrhosis (PBC) anti-Nup210 antibodies correlate with progression toward end stage liver disease. Nup210 is possibly a destructive autoimmune target of the disease. One idea for the loss of tolerance is the increased or abnormal expression of Nup210 in patients with PBC.[13]
Anti-mitochondrial, anti-centromere and anti-nup62 are also found in PBC.
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000132182 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030091 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Greber UF, Senior A, Gerace L (1990). "A major glycoprotein of the nuclear pore complex is a membrane-spanning polypeptide with a large lumenal domain and a small cytoplasmic tail". EMBO J. 9 (5): 1495–502. doi:10.1002/j.1460-2075.1990.tb08267.x. PMC 551841. PMID 2184032.
- ^ Wozniak RW, Blobel G (1992). "The single transmembrane segment of gp210 is sufficient for sorting to the pore membrane domain of the nuclear envelope". J. Cell Biol. 119 (6): 1441–9. doi:10.1083/jcb.119.6.1441. PMC 2289754. PMID 1281815.
- ^ Favreau C, Worman HJ, Wozniak RW, Frappier T, Courvalin JC (1996). "Cell cycle-dependent phosphorylation of nucleoporins and nuclear pore membrane protein Gp210". Biochemistry. 35 (24): 8035–44. doi:10.1021/bi9600660. PMID 8672508.
- ^ Favreau C, Bastos R, Cartaud J, Courvalin JC, Mustonen P (2001). "Biochemical characterization of nuclear pore complex protein gp210 oligomers". Eur. J. Biochem. 268 (14): 3883–9. doi:10.1046/j.1432-1327.2001.02290.x. PMID 11453980.
- ^ Yang L, Guan T, Gerace L (1997). "Integral membrane proteins of the nuclear envelope are dispersed throughout the endoplasmic reticulum during mitosis". J. Cell Biol. 137 (6): 1199–210. doi:10.1083/jcb.137.6.1199. PMC 2132536. PMID 9182656.
- ^ Bodoor K, Shaikh S, Salina D, et al. (1999). "Sequential recruitment of NPC proteins to the nuclear periphery at the end of mitosis". J. Cell Sci. 112 (13): 2253–64. doi:10.1242/jcs.112.13.2253. PMID 10362555.
- ^ Cohen M, Feinstein N, Wilson KL, Gruenbaum Y (2003). "Nuclear pore protein gp210 is essential for viability in HeLa cells and Caenorhabditis elegans". Mol. Biol. Cell. 14 (10): 4230–7. doi:10.1091/mbc.E03-04-0260. PMC 207014. PMID 14517331.
- ^ Onischenko EA, Crafoord E, Hallberg E (2007). "Phosphomimetic mutation of the mitotically phosphorylated serine 1880 compromises the interaction of the transmembrane nucleoporin gp210 with the nuclear pore complex". Exp. Cell Res. 313 (12): 2744–51. doi:10.1016/j.yexcr.2007.05.011. hdl:10616/41278. PMID 17559836.
- ^ Nakamura M, Takii Y, Ito M, et al. (2006). "Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis". J. Autoimmun. 26 (2): 138–45. doi:10.1016/j.jaut.2005.10.007. PMID 16337775.