Publication Date:
2005-05-10
Description:
Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology, and up to 20% of patients on dialysis have been diagnosed with it. Here we show that a large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion-channel protein transient receptor potential cation channel 6 (TRPC6). The proline-to-glutamine substitution at position 112, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II and appears to alter the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytoskeletal and structural proteins in proteinuric kidney diseases. Our findings suggest an alternative mechanism for the pathogenesis of glomerular disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winn, Michelle P -- Conlon, Peter J -- Lynn, Kelvin L -- Farrington, Merry Kay -- Creazzo, Tony -- Hawkins, April F -- Daskalakis, Nikki -- Kwan, Shu Ying -- Ebersviller, Seth -- Burchette, James L -- Pericak-Vance, Margaret A -- Howell, David N -- Vance, Jeffery M -- Rosenberg, Paul B -- R01 DK074748/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2005 Jun 17;308(5729):1801-4. Epub 2005 May 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. michelle.winn@duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15879175" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Substitution
;
Angiotensin II/metabolism/pharmacology
;
Calcium/metabolism
;
Calcium Channels/chemistry/*genetics/metabolism
;
Calcium Signaling
;
Carbachol/pharmacology
;
Cell Line
;
Cell Membrane/metabolism
;
Chromosomes, Human, Pair 11/genetics
;
Exons
;
Female
;
GTP-Binding Protein alpha Subunits, Gq-G11/metabolism
;
Glomerulosclerosis, Focal Segmental/*genetics
;
Haplotypes
;
Humans
;
Kidney/metabolism
;
Kidney Glomerulus/metabolism
;
Kidney Tubules/metabolism
;
Male
;
*Mutation, Missense
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Patch-Clamp Techniques
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Pedigree
;
Receptor, Angiotensin, Type 1/genetics/metabolism
;
Sequence Analysis, DNA
;
Sodium/metabolism
;
TRPC Cation Channels
;
Transfection
;
Uridine Triphosphate/metabolism/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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