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Molecular and Cellular Biology, April 1999, p. 3136-3144, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Basolateral Sorting of Furin in MDCK Cells Requires
a Phenylalanine-Isoleucine Motif Together with an Acidic Amino
Acid Cluster
Thomas
Simmen,1
Massimo
Nobile,1
Juan S.
Bonifacino,2 and
Walter
Hunziker1,*
Institute of Biochemistry, BIL Biomedical
Research Center, University of Lausanne, CH-1066 Epalinges,
Switzerland,1 and Cell Biology and
Metabolism Branch, National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, Maryland
208922
Received 14 August 1998/Returned for modification 29 September
1998/Accepted 7 January 1999
Furin is a subtilisin-related endoprotease which processes a wide
range of bioactive proteins. Furin is concentrated in the trans-Golgi
network (TGN), where proteolytic activation of many precursor proteins
takes place. A significant fraction of furin, however, cycles among the
TGN, the plasma membrane, and endosomes, indicating that the
accumulation in the TGN reflects a dynamic localization process. The
cytosolic domain of furin is necessary and sufficient for TGN
localization, and two signals are responsible for retrieval of furin to
the TGN. A tyrosine-based (YKGL) motif mediates internalization of
furin from the cell surface into endosomes. An acidic cluster that is
part of two casein kinase II phosphorylation sites (SDSEEDE) is then
responsible for retrieval of furin from endosomes to the TGN. In
addition, the acidic EEDE sequence also mediates endocytic activity.
Here, we analyzed the sorting of furin in polarized epithelial cells.
We show that furin is delivered to the basolateral surface of MDCK
cells, from where a significant fraction of the protein can return to
the TGN. A phenylalanine-isoleucine motif together with the acidic EEDE
cluster is required for basolateral sorting and constitutes a novel
signal regulating intracellular traffic of furin.
*
Corresponding author. Mailing address: Institute of
Biochemistry, BIL Biomedical Research Center, University of Lausanne, CH-1066 Epalinges, Switzerland. Phone: 41 21 692 5737. Fax: 41 21 692 5705. E-mail: Walter.Hunziker{at}ib.unil.ch.
Molecular and Cellular Biology, April 1999, p. 3136-3144, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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