Inositol polyphosphate receptor and clathrin assembly protein AP-2 are related proteins that form potassium-selective ion channels in planar lipid bilayers

Anthony P. Timerman*, Martin M. Mayrleitner, Thomas J. Lukas, Christopher C. Chadwick, Akitsugu Saito, D. Martin Watterson, Hansgeorg Schindler, Sidney Fleischer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

We have previously described an inositol polyphosphate receptor (IPxRec), purified from detergent-solubilized bovine cerebellum microsomes, that displays potassium ion channel activity in planar lipid bilayers. We now find that the IPxRec is closely related to clathrin assembly protein AP-2. The IPxRec and AP-2 purified from bovine brain clathrin-coated vesicles share several structural and functional features: (i) similar subunit composition; each has four major polypeptides that have similar mobility (Mr values of 111,000, 100,000, 50,000, and 17,000) and relative intensity by SDS/PAGE analysis; (ii) similar size as studied by molecular sieve chromatography (Mr 400,000); (iii) identical N-terminal amino acid sequences for the Mr 50,000 subunits and Mr 111,000/100,000 doublets; (iv) immunoreactivity of the AP-2 Mr 111,000/100,000 doublet to polyclonal antibodies affinity purified against the doublet proteins of the IPxRec; (v) display of the in vitro diagnostic feature of assembly proteins - i.e., they induce the assembly of clathrin cages; and (vi) ion channel activity selective for potassium ions with the same unitary conductance when incorporated into planar lipid bilayers. One difference was found. AP-2 channels were not blocked by inositol 1,3,4,5-tetraphosphate as reported for IPx receptor channels. These studies suggest a possible connection between the IPx signaling pathways and receptor-mediated endocytosis.

Original languageEnglish (US)
Pages (from-to)8976-8980
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number19
DOIs
StatePublished - Oct 1 1992

Keywords

  • Clathrin-coated vesicles
  • Inositol 1,3,4,5-tetrakisphosphate
  • Receptor-mediated endocytosis
  • Signaling

ASJC Scopus subject areas

  • General

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