AP-1 and retromer play opposite roles in the trafficking of sortilin between the Golgi apparatus and the lysosomes

Canuel, Maryssa; Lefrançois, Stéphane; Zeng, Jibin; Morales, Carlos R.

doi:10.1016/j.bbrc.2007.12.015

Cited by 102 publications

(120 citation statements)

References 29 publications

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“…Upon truncation of the sortilin cytoplasmic tail, sortilin and BACE1 expression is decreased in the TGN and increased in the early endosomes. This is consistent with the fact that the sortilin cytoplasmic domain is required for retromerand/or GGA-mediated transport from the endosome to the TGN (27,30). To substantiate our immunocytochemistry results and verify a biochemical interaction using the same constructs that we used for confocal analyses, we performed a further co-immunoprecipitation experiment utilizing the GFP-tagged sortilin constructs (sortFL-GFP and sort⌬C-GFP) and CFP-tagged BACE1 (BACE1-CFP) (supplemental Fig.…”

Section: Deletion Of the Cytoplasmic Tail Of Sortilin Preserves The Isupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it has recently been found that sortilin interacts with retromer and is responsible for sortilin retrograde trafficking to the TGN (30). Evidence suggests that BACE1 also undergoes retrograde trafficking from the early endosomes to the TGN (10,30). Given that the sortilin cytoplasmic tail contains similar sorting motifs as the CI-MPR and appears to mimic the trafficking patterns and function of CI-MPR, which itself undergoes retromer transport, it is highly plausible that sortilin also participates in retrograde trafficking of specific cargo, interacting with the Vps35 or Vps26 component of the retromer complex to drive cargo selection (much like the Vps10p and retromer in yeast).…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that the sortilin cytoplasmic domain can convey Golgi localization and Golgi-endosome transport. Such a sorting and trafficking role for sortilin can be attributed to two motifs, a tyrosine-based YSVL motif and an acidic clusterdileucine motif, both appearing to contribute to the endocytosis and intracellular trafficking of sortilin (27)(28)(29)(30). These motifs are likewise found within the CI-MPR (the functional equivalent of Vps10p), which is responsible for transporting lysosomal enzymes from the Golgi to the lysosome and subsequently undergoes retrograde transport via retromer (31)(32)(33).…”

Section: Alzheimer Disease (Ad)mentioning

confidence: 99%

“…Furthermore, both sortilin and BACE1 follow a similar trafficking pattern in which both proteins are subjected to the retromer pathway (10,27,30). We therefore wanted to determine whether sortilin and BACE1 interact and exhibit similar subcellular distribution.…”

Section: The Analysis Of Vps10p Domain Family Members In Ad Postmortementioning

confidence: 99%

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BACE1 Retrograde Trafficking Is Uniquely Regulated by the Cytoplasmic Domain of Sortilin

Finan

Okada

Kim

2011

Journal of Biological Chemistry

103

107

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BACE1 (␤-site ␤-amyloid precursor protein (APP)-cleaving enzyme 1) mediates the first proteolytic cleavage of APP, leading to amyloid ␤-peptide (A␤) production. It has been reported that BACE1 intracellular trafficking, in particular endosometo-TGN sorting, is mediated by adaptor complexes, such as retromer and Golgi-localized ␥-ear-containing ARF-binding proteins (GGAs). Here we investigated whether sortilin, a Vps10p domain-sorting receptor believed to participate in retromer-mediated transport of select membrane cargoes, contributes to the subcellular trafficking and activity of BACE1. Our initial studies revealed increased levels of sortilin in post-mortem brain tissue of AD patients and that overexpression of sortilin leads to increased BACE1-mediated cleavage of APP in cultured cells. In contrast, RNAi suppression of sortilin results in decreased BACE1-mediated cleavage of APP. We also found that sortilin interacts with BACE1 and that a sortilin construct lacking its cytoplasmic domain, which contains putative retromer sorting motifs, remains bound to BACE1. However, expression of this truncated sortilin redistributes BACE1 from the trans-Golgi network to the endosomes and substantially reduces the retrograde trafficking of BACE1. Site-directed mutagenesis and chimera experiments reveal that the cytoplasmic tail of sortilin, but not those from other VPS10p domain receptors (e.g. SorCs1b and SorLA), plays a unique role in BACE1 trafficking. Our studies suggest a new function for sortilin as a modulator of BACE1 retrograde trafficking and subsequent generation of A␤.

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Section: Deletion Of the Cytoplasmic Tail Of Sortilin Preserves The Isupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Alzheimer Disease (Ad)mentioning

confidence: 99%

Section: The Analysis Of Vps10p Domain Family Members In Ad Postmortementioning

confidence: 99%

See 3 more Smart Citations

BACE1 Retrograde Trafficking Is Uniquely Regulated by the Cytoplasmic Domain of Sortilin

Finan

Okada

Kim

2011

Journal of Biological Chemistry

103

107

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Akt may associate with insulin‐responsive vesicles via interaction with sortilin

Zaarur,

Meriin,

Singh

et al. 2023

FEBS Letters

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Insulin‐responsive vesicles (IRVs) deliver the glucose transporter Glut4 to the plasma membrane in response to activation of the insulin signaling cascade: insulin receptor–IRS–PI3 kinase–Akt–TBC1D4–Rab10. Previous studies have shown that Akt, TBC1D4, and Rab10 are compartmentalized on the IRVs. Although functionally significant, the mechanism of Akt association with the IRVs remains unknown. Using pull‐down assays, immunofluorescence microscopy, and cross‐linking, we have found that Akt may be recruited to the IRVs via the interaction with the juxtamembrane domain of the cytoplasmic C terminus of sortilin, a major IRV protein. Overexpression of full‐length sortilin increases insulin‐stimulated phosphorylation of TBC1D4 and glucose uptake in adipocytes, while overexpression of the cytoplasmic tail of sortilin has the opposite effect. Our findings demonstrate that the IRVs represent both a scaffold and a target of insulin signaling.

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Complicated trafficking behaviors involved in paradoxical regulation of sortilin in lipid metabolism

Sun

Yang

Xie

et al. 2019

Journal Cellular Physiology

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This review aims to summarize and discuss the most recent advances in our understanding of the underlying mechanisms of the paradoxical effects of sortilin on lipid metabolism. The vacuolar protein sorting 10 protein (Vps10p) domain in the sortilin protein is responsible for substrate binding. Its cytoplasmic tail interacts with adaptor molecules, and modifications can determine whether sortilin trafficking occurs via the anterograde or retrograde pathway. The complicated trafficking behaviors likely contribute to the paradoxical roles of sortilin in lipid metabolism. The anterograde pathway of sortilin trafficking in hepatocytes, enterocytes, and peripheral cells likely causes an increase in plasma lipid levels, while the retrograde pathway leads to the opposite effect. Hepatocyte sortilin functions via the anterograde or retrograde pathway in a complicated and paradoxical manner to regulate apoB‐containing lipoprotein metabolism. Clarifying the regulatory mechanisms underlying the trafficking behaviors of sortilin is necessary and may lead to artificial sortilin intervention as a potential therapeutic strategy for lipid disorder diseases. Conclusively, the paradoxical regulation of sortilin in lipid metabolism is likely due to its complicated trafficking behaviors.

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AP-1 and retromer play opposite roles in the trafficking of sortilin between the Golgi apparatus and the lysosomes

Cited by 102 publications

References 29 publications

BACE1 Retrograde Trafficking Is Uniquely Regulated by the Cytoplasmic Domain of Sortilin

BACE1 Retrograde Trafficking Is Uniquely Regulated by the Cytoplasmic Domain of Sortilin

Akt may associate with insulin‐responsive vesicles via interaction with sortilin

Complicated trafficking behaviors involved in paradoxical regulation of sortilin in lipid metabolism

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