Multiple cytoplasmic signals direct the intracellular trafficking of chicken kidney AE1 anion exchangers in MDCK cells

Tracy L. Adair-Kirk, Frank C. Dorsey, John V. Cox

Research output: Contribution to journalReview article

13 Citations (Scopus)

Abstract

AE1/Fc receptor chimeras have been used to define the sequences that direct the basolateral sorting, recycling and cytoskeletal association of the chicken AE1-4 anion exchanger in MDCK cells. These analyses revealed that amino acids 1-63 of AE1-4 were sufficient to redirect a cytoplasmic tailless murine IgG FcRII B2 receptor from the apical to the basolateral membrane of MDCK cells, where Fc1-63 associated with elements of the actin cytoskeleton. In contrast to Fc1-63, chimeras containing amino acids 1-37 (Fc1-37) or 38-63 (Fc38-63) of AE1-4 accumulated in intracellular membrane compartments that overlapped late endosomes and the trans-Golgi network (TGN), respectively. Internalization assays indicated that the patterns of localization observed for Fc1-37 and Fc38-63 resulted from the recycling of these chimeras from the cell surface. These assays further indicated that Fc1-37 and Fc38-63 each possess a basolateral sorting activity. Mutagenesis studies revealed that the endocytic and basolateral sorting activities in Fc1-37 are dependent upon serine 25, which is located in a sequence similar to a sorting signal in the polymeric immunoglobulin receptor. In addition, the sorting activities associated with Fc38-63 were dependent upon tyrosine 47 and leucine 50. These residues resided within the sequence, YVEL, which matches the YXXφ motif (where X is any amino acid and φ is a hydrophobic residue) that functions as an endocytic and TGN recycling signal for other membrane proteins. Our data indicate that amino acids 1-63 of AE1-4 contain sorting and cytoskeletal binding activities that account for most of the properties previously associated with AE1-4 in MDCK cells. Furthermore, the alternative localization patterns exhibited by chimeras containing various combinations of these activities suggest that interplay between these cytoplasmic activities is critical for specifying AE1-4 localization in epithelial cells.

Original languageEnglish (US)
Pages (from-to)655-663
Number of pages9
JournalJournal of Cell Science
Volume116
Issue number4
DOIs
StatePublished - Feb 15 2003

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Erythrocyte Anion Exchange Protein 1
Madin Darby Canine Kidney Cells
Chickens
trans-Golgi Network
Kidney
Amino Acids
Recycling
Polymeric Immunoglobulin Receptors
Intracellular Membranes
Fc Receptors
Endosomes
Actin Cytoskeleton
Leucine
Mutagenesis
Serine
Tyrosine
Membrane Proteins
Immunoglobulin G
Epithelial Cells
Membranes

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Multiple cytoplasmic signals direct the intracellular trafficking of chicken kidney AE1 anion exchangers in MDCK cells. / Adair-Kirk, Tracy L.; Dorsey, Frank C.; Cox, John V.

In: Journal of Cell Science, Vol. 116, No. 4, 15.02.2003, p. 655-663.

Research output: Contribution to journalReview article

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