Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2557-2567 |
Number of pages | 11 |
Journal | EMBO Journal |
Volume | 21 |
Issue number | 11 |
DOIs | |
State | Published - Jun 3 2002 |
Externally published | Yes |
Keywords
- Arf6
- Clathrin-independent
- EHD1
- MHC class I
- Recycling
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology