| Deficiency of polycystin-2 reduces Ca2+ channel activity and cell proliferation in ADPKD lymphoblastoid cells. | |
| | |
MedLine Citation:
|
PMID: 15001556 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Polycystin-2 (PC2), encoded by the PKD2 gene, mutated in 10-15% of autosomal-dominant polycystic kidney disease (ADPKD) patients, is a Ca2+-permeable cation channel present in kidney epithelia and other tissues. As PC2 was found expressed in B-lymphoblastoid cells (LCLs) and Ca2+ signaling pathways are important regulators of B cell function activities, we investigated whether PC2 plays some role in B-LCLs. In LCLs, PC2 was found mainly in ER membranes but ~8 times less than in kidney HEK293 cells. The same reductions were found in PKD2 and PKD1 RNA; thus, PKD genes maintained, in LCLs, the same reciprocal proportion as they do in kidney cells. In LCLs obtained from subjects carrying PKD2 mutations (PKD2-LCLs) and showing reduced PC2 levels, intracellular Ca2+ concentrations evoked by platelet-activating factor (PAF), were significantly lower than in non-PKD-LCLs. This reduction was also found in PKD1-LCLs but without PC2 reductions. Likewise, cell proliferation, which is controlled by Ca2+, was reduced in PKD2- and PKD1-LCLs. Moreover, in LCLs with PKD2 nonsense mutations, aminoglycoside antibiotics reduced the PC2 defect by promoting readthrough of stop codons. Therefore, PC2 and PC1 are functionally expressed in LCLs, which provide a model, easily obtainable from ADPKD patients, to study PKD gene expression and function. |
| | |
Authors:
|
Gianluca Aguiari; Manuela Banzi; Stefania Gessi; Yiqiang Cai; Emanuela Zeggio; Elisa Manzati; Roberta Piva; Elisabetta Lambertini; Luisa Ferrari; Dorien J Peters; Francesco Lanza; Peter C Harris; Pier Andrea Borea; Stefan Somlo; Laura Del Senno |
Related Documents
:
|
9658196 - Molecular basis for the lack of herg k+ channel block-related cardiotoxicity by the h1 ... 15120636 - Potent inhibition of human cardiac potassium (herg) channels by the anti-estrogen agent... 6264086 - Possible reduction of surface charge by a mutation in paramecium tetraurelia. 22422396 - Suppression of human detrusor smooth muscle excitability and contractility via pharmaco... 12228456 - Identification of the plasma membrane ca2+-atpase and of its autoinhibitory domain. 11124976 - Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei. |
Publication Detail:
|
Type: Comparative Study; Journal Article Date: 2004-03-04 |
Journal Detail:
|
Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 18 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2004 May |
Date Detail:
|
Created Date: 2004-04-30 Completed Date: 2004-09-28 Revised Date: 2012-02-22 |
Medline Journal Info:
|
Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
|
Languages: eng Pagination: 884-6 Citation Subset: IM |
Affiliation:
|
Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Substitution B-Lymphocytes / metabolism* Calcium / metabolism* Calcium Signaling* / genetics Cell Division / genetics Cell Line, Transformed Codon, Nonsense Endoplasmic Reticulum / chemistry Gentamicins / pharmacology Humans Ion Transport / genetics Kidney / pathology Membrane Proteins / deficiency*, genetics, physiology Mutation, Missense Organ Specificity Platelet Activating Factor / pharmacology Point Mutation Polycystic Kidney, Autosomal Dominant / genetics, metabolism*, pathology Proteins / genetics, physiology RNA, Messenger / biosynthesis Suppression, Genetic / drug effects TRPP Cation Channels |
| Grant Support | |
ID/Acronym/Agency:
|
E.1250//Telethon |
| Chemical | |
Reg. No./Substance:
|
0/Codon, Nonsense; 0/Gentamicins; 0/Membrane Proteins; 0/Platelet Activating Factor; 0/Proteins; 0/RNA, Messenger; 0/TRPP Cation Channels; 0/polycystic kidney disease 1 protein; 0/polycystic kidney disease 2 protein; 58152-03-7/isepamicin; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan-po...
Next Document: A small molecule CFTR inhibitor produces cystic fibrosis-like submucosal gland fluid secretions in n...