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| Subject Categories: Membranes & Transport | Immunology |
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| The EMBO Journal
(2002) 21, 2557–2567, doi: 10.1093/emboj/21.11.2557 |
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| A tubular EHD1-containing compartment involved in the recycling of major histocompatibility complex class I molecules to the plasma membrane |
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| Steve Caplan1, Naava Naslavsky2, Lisa M. Hartnell1, Robert Lodge1, Roman S. Polishchuk3, Julie G. Donaldson2 and Juan S. Bonifacino1 |
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1 Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA 2 Laboratory of Cell Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA 3 Department of Cell Biology and Oncology, Istituto di Ricerche Farmacologiche 'Mario Negri', Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy To whom correspondence should be addressed Juan S. Bonifacino, juan@helix.nih.gov Received 18 February 2002; Revised 10 April 2002; Accepted 10 April 2002. |
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| Abstract |
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| The Eps15 homology (EH) domain-containing protein, EHD1, has recently been ascribed a role in the recycling of receptors internalized by clathrin-mediated endocytosis. A subset of plasma membrane proteins can undergo internalization by a clathrin-independent pathway regulated by the small GTP-binding protein ADP-ribosylation factor 6 (Arf6). Here, we report that endogenous EHD proteins, as well as transgenic tagged EHD1, are associated with long, membrane-bound tubules containing Arf6. EHD1 appears to induce tubule formation, which requires nucleotide cycling on Arf6 and intact microtubules. Mutations in the N-terminal P-loop domain or deletion of the C-terminal EH domain of EHD1 prevent association of EHD1 with tubules or induction of tubule formation. The EHD1 tubules contain internalized major histocompatibility complex class I (MHC-I) molecules that normally traffic through the Arf6 pathway. Recycling assays show that overexpression of EHD1 enhances MHC-I recycling. These observations suggest an additional function of EHD1 as a tubule-inducing factor in the Arf6 pathway for recycling of plasma membrane proteins internalized by clathrin-independent endocytosis. |
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| Keywords: Arf6, clathrin-independent, EHD1, MHC class I, recycling |
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