DOI: 10.1073/pnas.93.24.14030. Biochemical characterization and intracellular localization of the Menkes disease protein

Biochemical characterization and intracellular localization of the Menkes disease protein

10.1073/pnas.93.24.14030

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Menkes disease is a fatal neurodegenerative disorder of childhood due to the absence or dysfunction of a putative copper-transporting P-type ATPase encoded on the X chromosome. To elucidate the biosynthesis and subcellular localization of this protein, polyclonal antisera were generated against a bacterial fusion protein encoding the 4th to 6th copper-binding domains in the amino terminus of the human Menkes protein. RNA blot analysis revealed abundant Menkes gene expression in several cell lines, and immunoblotting studies utilizing this antiserum readily detected a 178-kDa protein in lysates from these cells. Pulse–chase studies indicate that this protein is synthesized as a single-chain polypeptide which is modified by N-linked glycosylation to a mature endoglycosidase H-resistant form. Sucrose gradient fractionation of HeLa cell lysates followed by immunoblotting of individual fractions with antibodies to proteins of known intracellular location identified the Menkes ATPase in fractions similar to those containing the cation-independent mannose-6-phosphate receptor. Consistent with this observation, confocal immunofluorescence studies of these same cells localized this protein to the trans-Golgi network and a vesicular compartment with no expression in the nucleus or on the plasma membrane. Taken together, these data provide a unique model of copper transport into the secretory pathway of mammalian cells which is compatible with clinical observations in affected patients and with recent data on homologous proteins identified in prokaryotes and yeast.

Bibliography

Yamaguchi, Y., Heiny, M. E., Suzuki, M., & Gitlin, J. D. (1996). Biochemical characterization and intracellular localization of the Menkes diseaseâprotein. Proceedings of the National Academy of Sciences, 93(24), 14030â14035.

Authors 4

Yukitoshi Yamaguchi (first)
Mark E. Heiny (additional)
Mariko Suzuki (additional)
Jonathan D. Gitlin (additional)

References 40 Referenced 166

J H Menkes, M Alter, G K Steigleder, D R Weakley, J H Sung Pediatrics 29, 764–769 (1962). / Pediatrics by Menkes J H (1962)
S G Kaler Adv Pediatrics 41, 263–304 (1994). (10.1016/S0065-3101(24)00096-3) / Adv Pediatrics by Kaler S G (1994)
10.1146/annurev.nu.15.070195.001453
10.1073/pnas.73.2.604
10.1007/BF00504364
10.1038/ng0193-7
10.1038/ng0193-14
10.1038/ng0193-20
10.1111/j.1365-2958.1993.tb00898.x
10.1016/0168-9525(94)90172-4
10.1016/S0021-9258(18)31455-8
10.1073/pnas.91.20.9651
10.1073/pnas.92.7.2632
10.1093/hmg/4.11.2117
10.1038/ng1293-327
10.1038/ng1293-344
10.1006/bbrc.1993.2471
10.1021/bi00591a005
10.1073/pnas.89.19.9079
10.1016/0378-1119(88)90005-4
10.1016/S0021-9258(19)67764-1
10.1016/S0021-9258(18)34425-9
10.1006/scel.1993.1007
10.1016/S0092-8674(88)80026-6
10.1083/jcb.108.6.2137
Hwang C. Sinslay A. J. & Lodish H. F. Science 257 1496–1502. (10.1126/science.1523409)
10.1016/S0021-9258(20)80767-4
10.1074/jbc.270.19.11543
10.1016/0092-8674(84)90413-6
10.1016/S0021-9258(17)42125-9
10.1016/S0021-9258(18)98505-4
10.1083/jcb.130.2.285
10.1074/jbc.271.24.14504
10.1073/pnas.92.9.3784
10.1038/ng0696-219
10.1006/geno.1995.1175
10.1016/0888-7543(95)80160-N
10.1038/ng1094-195
10.1038/ng0196-11
10.1038/ng0596-21

Dates

Type	When
Created	23 years ago (July 26, 2002, 10:35 a.m.)
Deposited	8 months, 2 weeks ago (Dec. 7, 2024, 5:30 p.m.)
Indexed	3 weeks, 5 days ago (July 30, 2025, 11:06 a.m.)
Issued	28 years, 9 months ago (Nov. 26, 1996)
Published	28 years, 9 months ago (Nov. 26, 1996)
Published Online	28 years, 9 months ago (Nov. 26, 1996)
Published Print	28 years, 9 months ago (Nov. 26, 1996)

Funders 0

None

BibTeX

@article{Yamaguchi_1996, title={Biochemical characterization and intracellular localization of the Menkes disease protein}, volume={93}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.93.24.14030}, DOI={10.1073/pnas.93.24.14030}, number={24}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Yamaguchi, Yukitoshi and Heiny, Mark E. and Suzuki, Mariko and Gitlin, Jonathan D.}, year={1996}, month=nov, pages={14030–14035} }

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