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A distinct class of endosome mediates clathrin-independent endocytosis to the Golgi complex

An Addendum to this article was published on 01 June 2002

Abstract

Mammalian cells endocytose a variety of proteins and lipids without utilising clathrin-coated pits1,2,3,4,5. Detailed molecular mechanisms for clathrin-independent endocytosis are unclear. Several markers for this process, including glycosphingolipid-binding bacterial toxin subunits such as cholera toxin B subunit (CTxB), and glycosyl-phosphatidyl-inositol (GPI)-anchored proteins, are found in detergent-resistant membrane fractions (DRMs), or 'lipid rafts'2,3,5,6,7. The Golgi complex constitutes one principal intracellular destination for these markers2. Uptake of both CTxB and GPI-anchored proteins may involve caveolae, small invaginations in the plasma membrane (PM)8,9,10,11,12,13. However, the identity of intermediate organelles involved in PM to Golgi trafficking, as well as the function of caveolins, defining protein components of caveolae12,13, are unclear. This paper shows that molecules which partition into DRMs and are endocytosed in a clathrin-independent fashion, accumulate in a discrete population of endosomes en route to the Golgi complex. These endosomes are devoid of markers for classical early and recycling endosomes, but do contain caveolin-1. Caveolin-1-positive endosomes are sites for the sorting of caveolin-1 away from Golgi-bound cargoes, although caveolin-1 itself is unlikely to have a direct function in PM to Golgi transport.

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Figure 1: Caveolin-1 is found in intracellular endosomes that label with CTxB, GPI-anchored proteins and SV40.
Figure 2: The CTxB subunit is delivered to the Golgi complex via caveolin-1-positive endosomes.
Figure 3: Caveolin-1 does not exchange between the PM and the Golgi complex.
Figure 4: Caveolin-1 is not required for trafficking of the CTxB subunit from the PM to the Golgi complex.

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Acknowledgements

Many thanks to P. Pipkin for assistance with SV40 infection, A. Helenius and L. Pelkmans for caveolin-1–GFP and the anti-SV40 antibodies, H. McMahon for the AP180-C construct, and H. Pelham and S. Munro for comments on the manuscript.

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Correspondence to Benjamin J. Nichols.

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Nichols, B. A distinct class of endosome mediates clathrin-independent endocytosis to the Golgi complex. Nat Cell Biol 4, 374–378 (2002). https://doi.org/10.1038/ncb787

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