Document Detail

Deficiency of polycystin-2 reduces Ca2+ channel activity and cell proliferation in ADPKD lymphoblastoid cells.
MedLine Citation:
PMID:  15001556     Owner:  NLM     Status:  MEDLINE    
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.
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
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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    
Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy.
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MeSH Terms
Amino Acid Substitution
B-Lymphocytes / metabolism*
Calcium / metabolism*
Calcium Signaling* / genetics
Cell Division / genetics
Cell Line, Transformed
Codon, Nonsense
Endoplasmic Reticulum / chemistry
Gentamicins / pharmacology
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
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

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