RGD Reference Report - Alpha-actinin associates with polycystin-2 and regulates its channel activity. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Alpha-actinin associates with polycystin-2 and regulates its channel activity.

Authors: Li, Q  Montalbetti, N  Shen, PY  Dai, XQ  Cheeseman, CI  Karpinski, E  Wu, G  Cantiello, HF  Chen, XZ 
Citation: Li Q, etal., Hum Mol Genet. 2005 Jun 15;14(12):1587-603. Epub 2005 Apr 20.
RGD ID: 7175289
Pubmed: PMID:15843396   (View Abstract at PubMed)
DOI: DOI:10.1093/hmg/ddi167   (Journal Full-text)

Polycystin-2 (PC2) is the product of the PKD2 gene, which is mutated in 10-15% patients of autosomal dominant polycystic kidney disease (ADPKD). PC2 is an integral transmembrane protein and acts as a calcium-permeable cation channel. The functional modulation of this channel by other protein partners remains largely unknown. In the present study, using a yeast two-hybrid approach, we discovered that both intracellular N- and C-termini of PC2 associate with alpha-actinins, actin-binding and actin-bundling proteins important in cytoskeleton organization, cell adhesion, proliferation and migration. The PC2-alpha-actinin association was confirmed by in vitro glutathione S-transferase pull-down and dot blot overlay assays. In addition, the in vivo interaction between endogenous PC2 and alpha-actinins was demonstrated by co-immunoprecipitation in human embryonic kidney 293 and Madin-Darby canine kidney (MDCK) cells, rat kidney and heart tissues and human syncytiotrophoblast (hST) apical membrane vesicles. Immunofluorescence experiments showed that PC2 and alpha-actinin were partially co-localized in epithelial MDCK and inner medullary collecting duct cells, NIH 3T3 fibroblasts and hST vesicles. We studied the functional modulation of PC2 by alpha-actinin in a lipid bilayer electrophysiology system using in vitro translated PC2 and found that alpha-actinin substantially stimulated the channel activity of reconstituted PC2. A similar stimulatory effect of alpha-actinin on PC2 was also observed when hST vesicles were reconstituted in lipid bilayer. Thus, physical and functional interactions between PC2 and alpha-actinin may play an important role in abnormal cell adhesion, proliferation and migration observed in ADPKD.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Actn1  (actinin, alpha 1)
Actn2  (actinin alpha 2)
Pkd2  (polycystin 2, transient receptor potential cation channel)


Additional Information