Mutation G805R in the transmembrane domain of the LDL receptor gene causes familial hypercholesterolemia by inducing ectodomain cleavage of the LDL receptor in the endoplasmic reticulum

FEBS Open Bio

Volumn 4, Issue , 2014, Pages 321-327

  Strøm, Thea Bismo ^a   Tveten, Kristian ^a   Laerdahl, Jon K ^a,b   Leren, Trond P ^a  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF OSLO   (Norway)

Author keywords

Endoplasmic reticulum; Familial hypercholesterolemia; LDL receptor; Metalloproteinase; Mutation; Transmembrane domain

Indexed keywords

BATIMASTAT; GAMMA SECRETASE; LOW DENSITY LIPOPROTEIN RECEPTOR; ARGININE; GLYCINE; METALLOPROTEINASE; PROLINE; SERINE;

ARTICLE; CELL LYSATE; CELL STRAIN HEPG2; CELL SURFACE; CULTURE MEDIUM; ENDOPLASMIC RETICULUM; EXON; FAMILIAL HYPERCHOLESTEROLEMIA; GENE FUNCTION; GENE MUTATION; HUMAN; HUMAN CELL; NUCLEOTIDE SEQUENCE; PRECURSOR; PRIORITY JOURNAL; PROTEIN CLEAVAGE; WESTERN BLOTTING; ALPHA HELIX; CONFOCAL LASER MICROSCOPY; CONTROLLED STUDY; ECTODOMAIN CLEAVAGE; ENDOPLASMIC RETICULUM MEMBRANE; GENE; HEPG2 CELL LINE; HYDROPHOBICITY; LOW DENSITY LIPOPROTEIN RECEPTOR GENE; PROTEIN DEGRADATION; PROTEIN DOMAIN; SEGREGATION ANALYSIS; TRANSMEMBRANE DOMAIN;

EID: 84897935750     PISSN: 22115463     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.fob.2014.03.007     Document Type: Article

References (33)

1. Goldstein J.L., Hobbs H.H., Brown M.S. Familial hypercholesterolemia. The metabolic & molecular basis of inherited disease 2001, 2863-2914. McGraw-Hill, New York. C. Scriver, A.L. Beaudet, W.S. Sly, D. Valle (Eds.).
2. Tolleshaug H., Goldstein J.L., Schneider W.J., Brown M.S. Posttranslational processing of the LDL receptor and its genetic disruption in familial hypercholesterolemia. Cell 1982, 30:715-724.
3. Brown M.S., Goldstein J.L. A receptor-mediated pathway for cholesterol homeostasis. Science 1986, 232:34-47.
4. Südhof T.C., Goldstein J.L., Brown M.S., Russell D.W. The LDL receptor gene: a mosaic of exons shared with different proteins. Science 1985, 228:815-822.
5. Hobbs H.H., Russell D.W., Brown M.S., Goldstein J.L. The LDL receptor locus in familial hypercholesterolemia: mutational analysis of a membrane protein. Annu. Rev. Genet. 1990, 24:133-170.
6. Koivisto U.M., Hubbard A.L., Mellman I. A novel cellular phenotype for familial hypercholesterolemia due to a defect in polarized targeting of LDL receptor. Cell 2001, 105:575-585.
7. Yamamoto T., Davis C.G., Brown M.S., Schneider W.J., Casey M.L., Goldstein J.L., Russell D.W. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell 1984, 39:27-38.
8. Leren T.P., Manshaus T., Skovholt U., Skodje T., Nossen I.E., Teie C., Sørensen S., Bakken K.S. Application of molecular genetics for diagnosing familial hypercholesterolemia in Norway. Semin. Vasc. Med. 2004, 4:75-85.
9. Update on activities at the Universal Protein Resource (UniProt) in 2013. Nucleic Acids Res. 2013, 41:D43-47. UniProt Consortium.
10. Flicek P., Ahmed I., Amode M.R., Barrell D., Beal K., Brent S., Carvalho-Silva D., Clapham P., Coates G., Fairley S., et al. Ensembl 2013. Nucleic Acids Res. 2013, 41:D48-D55.
11. White S.H., von Heijne G. The machinery of membrane protein assembly. Curr. Opin. Struct. Biol. 2004, 14:397-404.
12. Tveten K., Strøm T.B., Berge K.E., Leren T.P. PCSK9-mediated degradation of the LDL receptor generates a 17 kDa C-terminal LDL receptor fragment. J. Lipid. Res. 2013, 54:1560-1566.
13. Brown M.S., Ye J., Rawson R.B., Goldstein J.L. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 2000, 100:391-398.
14. Lal M., Caplan M. Regulated intramembrane proteolysis: signalling pathways and biological functions. Physiology 2011, 26:34-44.
15. Hubbard S.J. The structural aspects of limited proteolysis of native proteins. Biochim. Biophys. Acta 1998, 1382:191-206.
16. Brodsky J.L. Cleaning up: ER-associated degradation to the rescue. Cell 2012, 151:1163-1167.
17. Miura H., Tomoda H., Miura K., Takishima K., Omura S. Lactacystine increases LDL receptor level on HepG2 cells. Biochem. Biophys. Res. Commun. 1996, 227:684-687.
18. Begg M.J., Sturrock E.D., van der Westhuysen D.R. Soluble LDL-R are formed by cell surface cleavage in response to phorbol esters. Eur. J. Biochem. 2004, 271:524-533.
19. Tveten K., Strøm T.B., Cameron J., Holla O.L., Berge K.E., Leren T.P. Characterization of a naturally occurring degradation product of the LDL receptor. Mol. Genet. Metab. 2012, 105:149-154.
20. Lemberg M.K. Intramembrane proteolysis in regulated protein trafficking. Traffic 2011, 12:1109-1118.
21. Schow E.V., Freites J.A., Cheng P., Bernsel A., von Heijne G., White S.H., Tobias D.J. Arginine in membranes: the connection between molecular dynamics simulations and translocon-mediated insertion experiments. J. Membr. Biol. 2011, 239:35-48.
22. Vostrikov V.V., Hall B.A., Greathouse D.V., Koeppe R.E., Sansom M.S.P. Changes in transmembrane helix alignment by arginine residues revealed by solid-state NMR experiments and coarse-gained MD simulations. J. Am. Chem. Soc. 2010, 132:5803-5811.
23. Weber S., Saftig P. Ectodomain shedding and ADAMs in development. Development 2012, 139:3693-3709.
24. Fleig L., Bergbold N., Sahasrabudhe P., Geiger B., Kaltak L., Lemberg M.K. Ubiquitin-dependent intramembrane rhomboid protease promotes ERAD of membrane proteins. Cell 2012, 47:558-569.
25. Moin S.M., Urban S. Membrane immersion allows rhomboid proteases to achieve specificity by reading transmembrane segment dynamics. eLIFE 2012, 1:e00173.
26. MacArthur M., Thornton J.M. Influence of proline residues on protein conformation. J. Mol. Biol. 1991, 218:397-412.
27. Monsonego-Ornan E., Adar R., Feferman T., Segev O., Yayon A. The transmembrane mutation G308R in fibroblast growth factor receptor 3 uncouples ligand-mediated receptor activation from down-regulation. Mol. Cell. Biol. 2000, 20:516-522.
28. Eggers S.D.Z., Keswani S.C., Melli G., Cornblath D.R. Clinical and genetic description of a family with Charcot-Marie-Tooth disease type 1b from a transmembrane MPZ mutation. Muscle Nerve 2004, 29:867-869.
29. Sørensen S., Ranheim T., Bakken K.S., Leren T.P., Kulseth M.A. Retention of mutant low density lipoprotein receptor in endoplasmic reticulum (ER) leads to ER stress. J. Biol. Chem. 2006, 281:468-476.
30. Tveten K., Holla O.L., Ranheim T., Berge K.E., Leren T.P., Kulseth M.A. 4-Phenylbutyrate restores the functionality of a misfolded mutant low-density lipoprotein receptor. FEBS J. 2007, 274:1881-1893.
31. Strøm T.B., Tveten K., Leren T.P. PCSK9 acts as a chaperone for the LDL receptor in the endoplasmic reticulum. Biochem. J. 2013, 10.1042/BJ20130930.
32. Pitas R.E., Innerarity T.L., Weinstein J.N., Mahley R.W. Acetoacetylated lipoproteins used to distinguish fibroblasts from macrophages in vitro by fluorescence microscopy. Arteriosclerosis 1981, 1:177-185.
33. Cameron J., Holla O.L., Ranheim T., Kulseth M.A., Berge K.E., Leren T.P. Effect of mutations in the PCSK9 gene on the cell surface LDL receptors. Hum. Mol. Genet. 2006, 15:1551-1558.