Isoforms of the Lutheran/Basal Cell Adhesion Molecule Glycoprotein Are Differentially Delivered in Polarized Epithelial Cells
MAPPING OF THE BASOLATERAL SORTING SIGNAL TO A CYTOPLASMIC DI-LEUCINE MOTIF*
- Wassim El Nemer‡,
- Yves Colin‡,
- Chantal Bauvy§,
- Patrice Codogno§,
- Robin H. Fraser¶,
- Jean Pierre Cartron‡ and
- Caroline Le Van Kim‡‖
- From ‡INSERM U76, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75015 Paris, France,§INSERM U504, Hôpital Paul Brousse, Villejuif, France, and the ¶Scottish National Blood Transfusion Service, G2 5UA Glasgow, Scotland
Abstract
Lu and Lu(v13) are two glycoprotein (gp) isoforms that belong to the immunoglobulin superfamily and carry both the Lutheran (Lu) blood group antigens and the basal cell adhesion molecule epithelial cancer antigen. Lu (85 kDa) and Lu(v13) (78 kDa) gps, which differ only in the length of their cytoplasmic domain, are adhesion molecules that bind laminin. In nonerythroid tissues, the Lu/basal cell adhesion molecule antigens are predominantly expressed in the endothelium of blood vessel walls and in the basement membrane region of normal epithelial cells, whereas they exhibit a nonpolarized expression in some epithelial cancers. Here, we analyzed the polarization of Lu and Lu(v13) gps in epithelial cells by confocal microscopy and domain-selective biotinylation assays. Differentiated human colon carcinoma Caco-2 cells exhibited a polarized expression of endogenous Lu antigens associated with a predominant expression of the Lu isoform at the basolateral domain of the plasma membrane and a very low expression of the Lu(v13) isoform at both the apical and basolateral domains. Analysis of transfected Madin-Darby canine kidney cells revealed a basolateral expression of Lu gp and a nonpolarized expression of Lu(v13) gp. Delivery of Lu(v13) to both apical and basolateral surfaces showed similar kinetics, indicating that this isoform is directly transported to each surface domain. A dileucine motif at position 608–609, specific to the Lu isoform, was characterized as a dominant basolateral sorting signal that prevents Lu gp from taking the apical delivery pathway.
Footnotes
-
↵* This investigation was supported in part by INSERM.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵‖ To whom correspondence should be addressed. Tel.: 33-1-44-49-30-46; Fax: 33-1-43-06-50-19; E-mail: clvkim@infobiogen.fr.
-
↵2 W. El Nemer, Y. Colin, C. Bauvy, P. Codogno, R. H. Fraser, J. P. Cartron, and C. Le Van Kim, unpublished results.
- Abbreviations:
- Lu
-
Lutheran
- B-CAM
-
basal cell adhesion molecule
- gp
-
glycoprotein
- kb
-
kilobase(s)
- MoAb
-
monoclonal antibody
- MDCK
-
Madin-Darby canine kidney
- SABC
-
specific antibody binding capacity
-
- Received July 9, 1999.
- Revision received August 27, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
