Document Detail


Functional expression in yeast of the human secretory pathway Ca(2+), Mn(2+)-ATPase defective in Hailey-Hailey disease.
MedLine Citation:
PMID:  11741891     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The discovery and biochemical characterization of the secretory pathway Ca(2+)-ATPase, PMR1, in Saccharomyces cerevisiae, has paved the way for identification of PMR1 homologues in many species including rat, Caenorhabditis elegans, and Homo sapiens. In yeast, PMR1 has been shown to function as a high affinity Ca(2+)/Mn(2+) pump and has been localized to the Golgi compartment where it is important for protein sorting, processing, and glycosylation. However, little is known about PMR1 homologues in higher organisms. Loss of one functional allele of the human gene, hSPCA1, has been linked to Hailey-Hailey disease, characterized by skin ulceration and improper keratinocyte adhesion. We demonstrate that expression of hSPCA1 in yeast fully complements pmr1 phenotypes of hypersensitivity to Ca(2+) chelators and Mn(2+) toxicity. Similar to PMR1, epitope-tagged hSPCA1 also resides in the Golgi when expressed in yeast or in chinese hamster ovary cells. (45)Ca(2+) transport by hSPCA1 into isolated yeast Golgi vesicles shows an apparent Ca(2+) affinity of 0.26 microm, is inhibitable by Mn(2+), but is thapsigargin-insensitive. In contrast, heterologous expression of vertebrate sarcoplasmic reticulum and plasma membrane Ca(2+)-ATPases in yeast complement the Ca(2+)- but not Mn(2+)-related phenotypes of the pmr1-null strain, suggesting that high affinity Mn(2+) transport is a unique feature of the secretory pathway Ca(2+)-ATPases.
Authors:
Van-Khue Ton; Debjani Mandal; Cordelia Vahadji; Rajini Rao
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2001-12-06
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-18     Completed Date:  2002-04-24     Revised Date:  2009-09-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6422-7     Citation Subset:  IM    
Affiliation:
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
CHO Cells
Calcium / metabolism
Calcium-Transporting ATPases / deficiency,  genetics,  metabolism
Chelating Agents / pharmacology
Cricetinae
Genetic Complementation Test
Glycosylation
Golgi Apparatus / enzymology
Humans
Kinetics
Manganese / metabolism,  pharmacology
Molecular Chaperones / genetics,  metabolism
Pemphigus, Benign Familial / enzymology,  genetics*
Phenotype
Phylogeny
Recombinant Proteins / metabolism
Saccharomyces cerevisiae / enzymology*
Saccharomyces cerevisiae Proteins*
Subcellular Fractions / enzymology
Transfection
Grant Support
ID/Acronym/Agency:
GM62142/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Chelating Agents; 0/Molecular Chaperones; 0/Recombinant Proteins; 0/Saccharomyces cerevisiae Proteins; 7439-96-5/Manganese; 7440-70-2/Calcium; EC 3.6.1.8/Calcium-Transporting ATPases; EC 3.6.3.8/ATP2C1 protein, human; EC 3.6.3.8/ATP2C2 protein, human; EC 3.6.3.8/SSC1 protein, S cerevisiae

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