A Di-hydrophobic Leu-Val Motif Regulates the Basolateral Localization of CD44 in Polarized Madin-Darby Canine Kidney Epithelial Cells (*)
- From the Department of Biology, Imperial College of Science, Technology and Medicine, Prince Consort Road, London SW7 2BB, United Kingdom
- § To whom correspondence should be addressed. h.sheikh{at}ic.ac.uk
Abstract
Both in vivo and in vitro the distribution of the resident plasma membrane adhesion protein, CD44, is restricted to the basolateral domain of polarized
epithelial cells, suggesting a role in interepithelial interactions. To determine how this localization might be regulated,
a range of CD44 cytoplasmic domain mutations were generated and a minimal 5 amino acid sequence, His
-Leu-Val-Asn-Lys
, was identified which when deleted results in expression of CD44 on the apical microvillal membrane. Further mutagenesis
throughout this regions pinpointed a critical di-hydrophobic motif, Leu
/Val
. The ability of wild type but not mutant CD44 cytoplasmic domains to redirect an apically targeted protein, placental alkaline
phosphatase, to the basolateral plasma membrane demonstrates that this sequence can function as a dominant localization signal.
This His
-Lys
sequence is spatially separate from other CD44 regulatory elements and as discussed here, a comparison with known basolateral
sorting sequences identified in other transmembrane proteins suggests that a distinct mechanism operates to retain resident
plasma membrane proteins in their correct plasma membrane subdomains.
Footnotes
-
↵* This work was supported by grants from the Medical Research Campaign and the Cancer Research Campaign. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵(
) The abbreviations used are:
- T-
-
tailless
- bp
-
base pair(s)
- WT
-
wild type
- MDCK
-
Madin-Darby canine kidney
- mAb
-
monoclonal antibody
- PLAP
-
placental alkaline phosphatase
- TGN
-
trans-Golgi network.
-
- Received December 26, 1995.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
