A common signal patch drives ap-1 protein-dependent golgi export of inwardly rectifying potassium channels

Xiangming Li, Bernardo Ortega, Boyoung Kim, Paul A. Welling

Research output: Contribution to journalArticle

Abstract

Nearly all members of the inwardly rectifying potassium (Kir) channel family share a cytoplasmic domain structure that serves as an unusual AP-1 clathrin adaptor-dependent Golgi export signal in one Kir channel, Kir2.1 (KCNJ2), raising the question whether Kir channels share a common Golgi export mechanism. Here we explore this idea, focusing on two structurally and functionally divergent Kir family members, Kir2.3 (KCNJ4) and Kir4.1/5.1 (KCNJ10/16), which have ∼50% amino identity. We found that Golgi export of both channels is blocked upon siRNA-mediated knockdown of the AP-1 γ subunit, as predicted for the common AP-1-dependent trafficking process. A comprehensive mutagenic analysis, guided by homology mapping in atomic resolution models of Kir2.1, Kir2.3, and Kir4.1/ 5.1, identified a common structure that serves as a recognition site for AP-1 binding and governs Golgi export. Larger than realized from previous studies with Kir2.1, the signal is created by a patch of residues distributed at the confluence of cytoplasmic N and C termini. The signal involves a stretch of hydrophobic residues from the C-terminal region that form a hydrophobic cleft, an adjacent cluster of basic residues within the N terminus, and a potential network of salt bridges that join the N- and C-terminal poles together. Because patch formation and AP-1 binding are dependent on proper folding of the cytoplasmic domains, the signal provides a common quality control mechanism at the Golgi for Kir channels. These findings identify a new proteostatic mechanism that couples protein folding of channels to forward trafficking in the secretory pathway.

Original languageEnglish (US)
Pages (from-to)14963-14972
Number of pages10
JournalJournal of Biological Chemistry
Volume291
Issue number29
DOIs
StatePublished - Jul 15 2016
Externally publishedYes

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Inwardly Rectifying Potassium Channel
Transcription Factor AP-1
Proteins
Vesicular Transport Adaptor Proteins
Cytoplasmic Structures
Protein folding
Secretory Pathway
Protein Folding
Quality Control
Small Interfering RNA
Quality control
Poles
Potassium
Salts
Drive

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A common signal patch drives ap-1 protein-dependent golgi export of inwardly rectifying potassium channels. / Li, Xiangming; Ortega, Bernardo; Kim, Boyoung; Welling, Paul A.

In: Journal of Biological Chemistry, Vol. 291, No. 29, 15.07.2016, p. 14963-14972.

Research output: Contribution to journalArticle

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