Intracellular trafficking of variant chicken kidney AE1 anion exchangers

Role of alternative NH2 termini in polarized sorting and Golgi recycling

Tracy L. Adair-Kirk, Kathleen H. Cox, John Cox

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The variant chicken kidney AE1 anion exchangers differ only at the NH2 terminus of their cytoplasmic domains. Transfection studies have indicated that the variant chicken AE1-4 anion exchanger accumulates in the basolateral membrane of polarized MDCK kidney epithelial cells, while the AE1-3 variant, which lacks the NH2-terminal 63 amino acids of AE1-4, primarily accumulates in the apical membrane. Mutagenesis studies have shown that the basolateral accumulation of AE1-4 is dependent upon two tyrosine residues at amino acids 44 and 47 of the polypeptide. Interestingly, either of these tyrosines is sufficient to direct efficient basolateral sorting of AE1-4. However, in the absence of both tyrosine residues, AE1-4 accumulates in the apical membrane of MDCK cells. Pulse-chase studies have shown that after delivery to the cell surface, newly synthesized AE1-4 is recycled to the Golgi where it acquires additional N-linked sugar modifications. This Golgi recycling activity is dependent upon the same cytoplasmic tyrosine residues that are required for the basolateral sorting of this variant transporter. Furthermore, mutants of AE1-4 that are defective in Golgi recycling are unable to associate with the detergent insoluble actin cytoskeleton and are rapidly turned over. These studies, which represent the first description of tyrosine-dependent cytoplasmic sorting signal for a type III membrane protein, have suggested a critical role for the actin cytoskeleton in regulating AE1 anion exchanger localization and stability in this epithelial cell type.

Original languageEnglish (US)
Pages (from-to)1237-1248
Number of pages12
JournalJournal of Cell Biology
Volume147
Issue number6
DOIs
StatePublished - Dec 13 1999

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Erythrocyte Anion Exchange Protein 1
Recycling
Tyrosine
Chickens
Kidney
Actin Cytoskeleton
Membranes
Epithelial Cells
Amino Acids
Madin Darby Canine Kidney Cells
Mutagenesis
Detergents
Transfection
Membrane Proteins
Peptides

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Intracellular trafficking of variant chicken kidney AE1 anion exchangers : Role of alternative NH2 termini in polarized sorting and Golgi recycling. / Adair-Kirk, Tracy L.; Cox, Kathleen H.; Cox, John.

In: Journal of Cell Biology, Vol. 147, No. 6, 13.12.1999, p. 1237-1248.

Research output: Contribution to journalArticle

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