Two different cytoplasmic tails direct isoforms of the membrane cofactor protein (CD46) to the basolateral surface of Madin-Darby canine kidney cells

Andrea Maisner, M. Kathryn Liszewski, John P. Atkinson, Reinhard Schwartz-Albiez, Georg Herrler

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Membrane cofactor protein (MCP; CD46), a widely distributed regulatory protein of the complement system, was analyzed for expression in polarized epithelial cells. Both a human and a simian (Vero C1008) cell line were found to contain endogenous MCP mainly on the basolateral surface. Transfected Madin-Darby canine kidney cells stably expressing human MCP delivered this protein also predominantly to the basolateral surface. A deletion mutant lacking the cytoplasmic tail was transported in a nonpolarized fashion, indicating that the targeting signal for the basolateral transport is located in the cytoplasmic domain. A characteristic feature of MCP is the presence of various isoforms that contain either of two different cytoplasmic tails as a consequence of alternative splicing. Two isoforms differing only in the cytoplasmic tail (tail 1 or 2) were analyzed for polarized expression in Madin-Darby canine kidney cells. Surface biotinylation, as well as confocal immunofluorescence microscopy, indicated that both proteins were transported to the basolateral surface. Because no sequence similarity has been observed, the two tails contain different basolateral targeting signals. A deletion mutant lacking the only tyrosine residue in tail 1 retained the polarized expression indicating that, in contrast to most basolateral sorting signals, the transport signal of the tail 1 isoform is not dependent on tyrosine. The maintenance of a targeting motif in two distinct cytoplasmic tails suggests that the basolateral expression of MCP in polarized epithelial cells is of physiological importance.

Original languageEnglish
Pages (from-to)18853-18858
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number31
DOIs
StatePublished - Oct 7 1996

Fingerprint Dive into the research topics of 'Two different cytoplasmic tails direct isoforms of the membrane cofactor protein (CD46) to the basolateral surface of Madin-Darby canine kidney cells'. Together they form a unique fingerprint.

  • Cite this