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© The Rockefeller University Press, 0021-9525/1997//929 $5.00
The Journal of Cell Biology, Volume 139, Number 4, , 1997 929-940


Article

The O-glycosylated Stalk Domain Is Required for Apical Sorting of Neurotrophin Receptors in Polarized MDCK Cells



Charles Yeaman*, Annick H. Le Gall*, Anne N. Baldwin{ddagger}, Laure Monlauzeur§, Andre Le Bivic§, and Enrique Rodriguez-Boulan*

* Dyson Vision Research Institute, Department of Ophthalmology, and Department of Cell Biology, Cornell University Medical College, New York 10021; {ddagger} Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305; and § Laboratoire de Genetique et Physiologie du Developpement, Unite Mixte de Recherche 9943 Faculte des Sciences de Luminy, 13288 Marseille, Cedex 09 France

Delivery of newly synthesized membrane-spanning proteins to the apical plasma membrane domain of polarized MDCK epithelial cells is dependent on yet unidentified sorting signals present in the luminal domains of these proteins. In this report we show that structural information for apical sorting of transmembrane neurotrophin receptors (p75NTR) is localized to a juxtamembrane region of the extracellular domain that is rich in O-glycosylated serine/threonine residues. An internal deletion of 50 amino acids that removes this stalk domain from p75NTR causes the protein to be sorted exclusively of the basolateral plasma membrane. Basolateral sorting stalk-minus p75NTR does not occur by default, but requires sequences present in the cytoplasmic domain. The stalk domain is also required for apical secretion of a soluble form of p75NTR, providing the first demonstration that the same domain can mediate apical sorting of both a membrane-anchored as well as secreted protein. However, the single N-glycan present on p75NTR is not required for apical sorting of either transmembrane or secreted forms.


Abbreviations used in this paper: N-CAM, neuronal cell adhesion molecule; pfu, plaque formation units.

Address all correspondence to Enrique Rodriguez-Boulan, Dyson Vision Research Institute, Room LC-300, Department of Ophthalmology, Cornell University Medical College, 1300 York Avenue, New York, NY 10021. Tel.: (212) 746-2272. Fax: (212) 746-8175. E-mail: boulan{at}med.cornell.edu

We are very grateful to W.J. Nelson (Stanford University Medical School, Stanford, CA) for critically reading the manuscript.



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