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J. Biol. Chem., Vol. 275, Issue 39, 30566-30572, September 29, 2000
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From the Departament de Biologia Cel.lular, Institut
d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS)
Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036-Barcelona, Spain
The endocytic compartment of eukaryotic cells is
a complex intracellular structure involved in sorting, processing, and
degradation of a great variety of internalized molecules. Recently, the
uptake through caveolae has emerged as an alternative internalization pathway, which seems to be directly related with some signal
transduction pathways. However, the mechanisms, molecules, and
structures regulating the transport of caveolin from the cell surface
into the endocytic compartment are largely unknown. In this study,
normal quiescent fibroblasts (normal rat kidney (NRK)) were used to
demonstrate that epidermal growth factor causes partial redistribution
of caveolin from the cell surface into a cellubrevin early endocytic compartment. Treatment of NRK cells with cytochalasin D or latrunculin A inhibits this pathway and the concomitant activation of Mek and
mitotic-activated protein (MAP) kinase; however, if cells were
pre-treated with filipin, cytochalasin D does not inhibit the
phosphorylation of MAP kinase induced by epidermal growth factor. From
these results we conclude that in NRK cells the intact actin
cytoskeleton is necessary for the EGF-mediated transport of caveolin
from the cell surface into the early endocytic compartment and the
activation of MAP kinase pathway.
Epidermal Growth Factor-mediated Caveolin Recruitment to Early
Endosomes and MAPK Activation
ROLE OF CHOLESTEROL AND ACTIN CYTOSKELETON*
,
*
This study was funded by Ministerio de Educacion y Cultura
Grant PM96-0083 (to C. E.).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.
Present address: Dept. of Physiology and Pharmacology, University
of Queensland, Brisbane Qld 4072 Australia.
§
To whom correspondence should be addressed. Tel.:
34-94-4021908; Fax: 34-93-4021907; E-mail:
enrich@medicina.ub.es.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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