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PMID:17944866

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Citation

Li, Q, Dai, XQ, Shen, PY, Wu, Y, Long, W, Chen, CX, Hussain, Z, Wang, S and Chen, XZ (2007) Direct binding of alpha-actinin enhances TRPP3 channel activity. J. Neurochem. 103:2391-400

Abstract

Transient receptor potential (TRP) polycystin 2 and 3 (TRPP2 and 3) are homologous members of the TRP superfamily of cation channels but have different physiological functions. TRPP2 is part of a flow sensor, and is defective in autosomal dominant polycystic kidney disease and implicated in left-right asymmetry development. TRPP3 is reported to implicate in sour tasting in bipolar cells of taste buds of the tongue and in the regulation of pH-sensitive action potential in neurons surrounding the central canal of spinal cord. TRPP3 is present in both excitable and non-excitable cells in various tissues, such as retina, brain, heart, testis, and kidney, but its common and cell type-specific functional characteristics remain largely unknown. In this study, we investigated physical and functional interactions between TRPP3 and alpha-actinin, an actin-bundling protein known to regulate several types of ion channels. We employed planer lipid bilayer electrophysiology system to study the function of TRPP3 channel that was affinity-purified from Madin-Darby canine kidney cells. Upon reconstitution in bilayer, TRPP3 exhibited cation channel activities that were substantially augmented by alpha-actinin. The TRPP3-alpha-actinin association was documented by co-immunoprecipitation using native cells and tissues, yeast two-hybrid, and in vitro binding assays. Further, TRPP3 was abundantly present in mouse brain where it associates with alpha-actinin-2. Taken together, alpha-actinin not only attaches TRPP3 to the cytoskeleton but also up-regulates TRPP3 channel function. It remains to be determined whether the TRPP3-alpha-actinin interaction is relevant to acid sensing and other functions in neuronal and non-neuronal cells.

Links

PubMed Online version:10.1111/j.1471-4159.2007.04940.x

Keywords

Actin Cytoskeleton/metabolism; Actinin/metabolism; Animals; Calcium Channels/metabolism; Cell Line; Cell Membrane/metabolism; Cytoskeleton/metabolism; Dogs; Humans; Membrane Potentials/physiology; Neurons, Afferent/metabolism; Protein Binding/physiology; Rabbits; Receptors, Cell Surface/metabolism; TRPP Cation Channels/metabolism; Up-Regulation/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ACTN1

enables

GO:0044325: transmembrane transporter binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9P0L9

F

Seeded From UniProt

complete

HUMAN:ACTN2

enables

GO:0044325: transmembrane transporter binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9P0L9

F

Seeded From UniProt

complete

HUMAN:PK2L1

located_in

GO:0005886: plasma membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PK2L1

located_in

GO:0043231: intracellular membrane-bounded organelle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PK2L1

enables

GO:0051371: muscle alpha-actinin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35609

F

Seeded From UniProt

complete

HUMAN:PK2L1

enables

GO:0005261: cation channel activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PK2L1

part_of

GO:0005886: plasma membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PK2L1

part_of

GO:0043231: intracellular membrane-bounded organelle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PK2L1

enables

GO:0051393: alpha-actinin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12814

F

Seeded From UniProt

complete

See also

References

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