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Targeting of transmembrane and GPI-anchored forms of N-CAM to opposite domains of a polarized epithelial cell

Nature volume 353, pages 76–77 (1991)Cite this article

Abstract

THE calcium-independent neural cell adhesion molecule N-CAM is expressed transiently during development in many tissues, including epithelia1. The three naturally occurring principal isoforms2,3 of N-CAM differ in the way in which they associate with the membrane and in their cytoplasmic domains4. These isoforms are generated by developmentally regulated alternative splicing of a single gene4–6: the large cytoplasmic domain (Id) form (relative molecular mass 180,000 (Mr 180K)) is specific for post-mitotic neurons; the 120K small cytoplasmic domain (ssd) and 140K small surface domain (sd) forms also occur on other cell types7. One function of the different isoforms could be to specify cellular localization; for example, glycosyl phosphatidyl inositol (GPI)-membrane anchoring acts as a targeting signal for expression on the apical surface of polarized epithelial cells8,9. Neurons and epithelial cells may use similar mechanisms for polarizing their plasma membrane proteins10,11. We have therefore investigated the targeting of GPI-anchored (ssd N-CAM, 120K) and transmembrane forms of N-CAM (sd N-CAM, 140K; Id N-CAM, 180K) by comparing the expression of each after transfection of the appropriate complementary DNAs into polarized epithelial cells. We find that isoforms with alternative modes of membrane association are targeted to different surfaces of polarized epithelial cells: ssd N-CAM is expressed on the apical surface, whereas sd and Id N-CAM are expressed on the basolateral surface. These results suggest that the different isoforms of N-CAM determine their own diverse cellular destinations. They also support the hypothesis that the GPI anchor acts as an apical targeting signal in epithelia.

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Author notes

  1. Bruce A. Cunningham and Gerald M. Edelman: Department of Developmental and Molecular Biology, Rockefeller University, New York, New York 10021, USA

Authors and Affiliations

  1. Department of Cell Biology and Anatomy, Cornell University Medical College, 1300 York Avenue, New York, New York, 10021, USA

    Sharon K. Powell, Bruce A. Cunningham, Gerald M. Edelman & Enrique Rodriguez-Boulan

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  1. Sharon K. Powell
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  2. Bruce A. Cunningham
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  3. Gerald M. Edelman
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  4. Enrique Rodriguez-Boulan
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Powell, S., Cunningham, B., Edelman, G. et al. Targeting of transmembrane and GPI-anchored forms of N-CAM to opposite domains of a polarized epithelial cell. Nature 353, 76–77 (1991). https://doi.org/10.1038/353076a0

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