Journal
TRAFFIC
Volume 8, Issue 12, Pages 1873-1886Publisher
WILEY
DOI: 10.1111/j.1600-0854.2007.00652.x
Keywords
EHD1; endosome; Golgi; membrane; retrieval; retromer; tubule
Categories
Funding
- MRC [G117/452] Funding Source: UKRI
- Medical Research Council [G117/452] Funding Source: researchfish
- Medical Research Council [G117/452] Funding Source: Medline
Ask authors/readers for more resources
Endosome-to-Golgi retrieval of the cation-independent mannose 6-phosphate receptor (CIMPR) requires the function of the retromer complex. Retromer is localized to endosomes and comprises two distinct sub complexes: the vacuolar protein sorting 35/29/26 sub complex that binds cargo and the sorting nexin (SNX)1/2 sub complex that tubulates endosomal membranes. To identify up- or down-stream regulatory factors of retromer, a comparative proteomic strategy was employed. Protein profiles of endosomally enriched membranes, from either wild-type or retromer-deficient mouse cells, were compared to identify proteins with either elevated or reduced expression levels. Eps15 homology domain-containing protein-1 (EHD1) was identified in endosomally enriched membrane fractions from retromer-deficient cells and was found to be approximately threefold upregulated in the absence of retromer. EHD1 is localized to tubular and vesicular endosomes, partially colocalizes with retromer and is associated with retromer in vivo. Mutation of the nucleotide-binding P-loop of EHD1 results in a dominant-negative effect upon retromer localization and endosome-to-Golgi retrieval, while loss of EHD1 expression by RNA interference destabilizes SNX1-positive tubules and inhibits endosome-to-Golgi retrieval. The interaction between EHD1 and retromer and the requirement for EHD1 to stabilize SNX1-tubules establish EHD1 as a novel facilitating component of endosome-to-Golgi retrieval.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available