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Interactions between EHD Proteins and Rab11-FIP2: A Role for EHD3 in Early Endosomal Transport

Naslavsky, Naava, Rahajeng, Juliati, Sharma, Mahak, Jović, Marko, Caplan, Steve·2006·Molecular Biology of the Cell
DOI 10.1091/mbc.e05-05-0466
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Abstract

Eps15 homology domain (EHD) 1 enables membrane recycling by controlling the exit of internalized molecules from the endocytic recycling compartment (ERC) en route to the plasma membrane, similar to the role described for Rab11. However, no physical or functional connection between Rab11 and EHD-family proteins has been demonstrated yet, and the mode by which they coordinate their regulatory activity remains unknown. Here, we demonstrate that EHD1 and EHD3 (the closest EHD1 paralog), bind to the Rab11-effector Rab11-FIP2 via EH–NPF interactions. The EHD/Rab11-FIP2 associations are affected by the ability of the EHD proteins to bind nucleotides, and Rab11-FIP2 is recruited to EHD-containing membranes. These results are consistent with a coordinated role for EHD1 and Rab11-FIP2 in regulating exit from the ERC. However, because no function has been attributed to EHD3, the significance of its interaction with Rab11-FIP2 remained unclear. Surprisingly, loss of EHD3 expression prevented the delivery of internalized transferrin and early endosomal proteins to the ERC, an effect differing from that described upon EHD1 knockdown. Moreover, the subcellular localization of Rab11-FIP2 and endogenous Rab11 were altered upon EHD3 knockdown, with both proteins absent from the ERC and retained in the cell periphery. The results presented herein promote a coordinated role for EHD proteins and Rab11-FIP2 in mediating endocytic recycling and provide evidence for the function of EHD3 in early endosome to ERC transport.

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  • The addition of fatty acids induces formation of large, detectable lipid droplets in non-adipocyte cells.

    “the addition of fatty acids is known to induce formation of large, detectable lipid droplets [25,26].”

    From EHD1 regulates cholesterol homeostasis and lipid droplet storage (2007) · cites this paper as [25]

    The Results passages on EHD3 and transferrin trafficking (Figures 5–6; page unavailable) describe enlarged early endosomal structures, not lipid droplets. Searches for fatty-acid addition and lipid-droplet formation found no passage in our copy addressing the claim. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

  • EHD1 regulates the Rab11 endosome recycling compartment trafficking and binds to Rab11-FIP2, a Rab11 effector.

    “EHD1 regulates the Rab11 endosome recycling compartment trafficking and binds to Rab11-FIP2, a Rab11 effector118.”

    From Endocytic recycling protein EHD1 regulates primary cilia morphogenesis and SHH signaling during neural tube development (2016) · cites this paper as [118]

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Metadata

Authors
Naslavsky, N., Rahajeng, J., Sharma, M., Jović, M., & Caplan, S.
Affiliations
Department of Biochemistry and Molecular Biology and Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-5870
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2006-01
Volume
17
Issue
1
Pages
163-177
ISSN
  • 1059-1524
  • 1939-4586
DOI
10.1091/mbc.e05-05-0466
Cited by
171
References
3
Language
en

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