Lin-7 targets the Kir 2.3 channel on the basolateral membrane via a L27 domain interaction with CASK

Christine Alewine, Bo Young Kim, Vandana Hegde, Paul A. Welling

Research output: Contribution to journalArticlepeer-review

Abstract

Polarized expression of the Kir 2.3 channel in renal epithelial cells is influenced by the opposing activities of two different PDZ proteins. Mammalian Lin-7 (mLin-7) directly interacts with Kir 2.3 to coordinate basolateral membrane expression, whereas the tax interacting protein 1 (TIP-1), composed of a single PDZ domain, competes for interaction with mLin-7 and drives Kir 2.3 into the endocytic pathway. Here we show that the basolateral targeting function of mLin-7 depends on its L27 domain, which directs interaction with a cognate L27 domain in the basolateral membrane-anchoring protein, calcium/calmodulin- dependent serine protein kinase (CASK). In MDCK cells, the expression of an mLin-7 mutant that lacks the L27 domain displaced Kir 2.3 from the mLin-7/CASK complex and caused the channel to accumulate into large intracellular vesicles that partially colocalized with Rab-11. Conversely, transplantation of the mLin-7 L27 domain to TIP-1 conferred CASK interaction and basolateral targeting of Kir 2.3. Expression of the CASK L27 domain redistributed endogenous mLin-7 to an intracellular compartment and caused Kir 2.3 to accumulate in subapical endosomes. Taken together, these data support a model whereby mLin-7 acts as a PDZ-to-L27 adapter, mediating indirect association of Kir 2.3 with a basolateral membrane scaffold and thereby stabilizing Kir 2.3 at the basolateral membrane.

Original languageEnglish (US)
Pages (from-to)C1733-C1741
JournalAmerican Journal of Physiology - Cell Physiology
Volume293
Issue number6
DOIs
StatePublished - Dec 2007
Externally publishedYes

Keywords

  • Calcium/calmodulin-dependent serine protein kinase
  • Kidney
  • PDZ
  • Polarity
  • Scaffold

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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