Identification of a novel conserved sorting motif required for retromer-mediated endosome-to-TGN retrieval

Seaman, Matthew N.

doi:10.1242/jcs.009654

Cited by 228 publications

(307 citation statements)

References 36 publications

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“…3B). Additionally, a subtle, but reproducible level of growth was also seen for single mutants of Ile 86 , Leu 87 , and His 88 on slightly lower zinc conditions (supplemental Table 2). These Stv1p mutants were all tested on medium containing 100 mM Ca 2ϩ to ensure that a lack of zinc resistance was not due to loss of V-ATPase enzyme assembly and/or enzyme function; all single mutants tested showed identical growth on calcium as the control strain (supplemental Table 2).…”

Section: Mislocalization Of Stv1p-containing V-atpase Enzyme To the Vmentioning

confidence: 84%

Sorting of the Yeast Vacuolar-type, Proton-translocating ATPase Enzyme Complex (V-ATPase)

Finnigan

Cronan

Park

et al. 2012

Journal of Biological Chemistry

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Section: Mislocalization Of Stv1p-containing V-atpase Enzyme To the Vmentioning

confidence: 84%

Sorting of the Yeast Vacuolar-type, Proton-translocating ATPase Enzyme Complex (V-ATPase)

Finnigan

Cronan

Park

et al. 2012

Journal of Biological Chemistry

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“…To characterize the endocytosis of proteins with a range of important endocytic motifs, we used the well-described CD8 chimera system (28)(29)(30)(31). This system comprises a set of constructs, each with the extracellular and transmembrane domain of CD8 α-chain, with varying cytosolic domains.…”

Section: Resultsmentioning

confidence: 99%

Clathrin-mediated endocytosis is inhibited during mitosis

Fielding

Willox

Okeke

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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A long-standing paradigm in cell biology is the shutdown of endocytosis during mitosis. There is consensus that transferrin uptake is inhibited after entry into prophase and that it resumes in telophase. A recent study proposed that endocytosis is continuous throughout the cell cycle and that the observed inhibition of transferrin uptake is due to a decrease in available transferrin receptor at the cell surface, and not to a shutdown of endocytosis. This challenge to the established view is gradually becoming accepted. Because of this controversy, we revisited the question of endocytic activity during mitosis. Using an antibody uptake assay and controlling for potential changes in surface receptor density, we demonstrate the strong inhibition of endocytosis in mitosis of CD8 chimeras containing any of the three major internalization motifs for clathrin-mediated endocytosis (YXXΦ, [DE]XXXL[LI], or FXNPXY) or a CD8 protein with the cytoplasmic tail of the cationindependent mannose 6-phosphate receptor. The shutdown is not gradual: We describe a binary switch from endocytosis being "on" in interphase to "off" in mitosis as cells traverse the G 2 /M checkpoint. In addition, we show that the inhibition of transferrin uptake in mitosis occurs despite abundant transferrin receptor at the surface of HeLa cells. Our study finds no support for the recent idea that endocytosis continues during mitosis, and we conclude that endocytosis is temporarily shutdown during early mitosis.

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“…7A). The mutations we introduced to each motif have been previously identified as the key residues involved in their respective trafficking roles (27,49). The mutations we analyzed included a double mutation in the dileucine motif (L51A/L52A), a double mutation in the YSVL motif (Y14A/L17A), both of these alterations together (LL & YSVL), and a double mutation in the FLV motif (F9A/L10A).…”

Section: Mutagenesis Analysis Of Sortilin Reveals Two Cytoplasmic Motmentioning

confidence: 99%

“…Finally, SorCS1c also contains YXX⌽ and two LL-like motifs. Their function is undetermined (46,49,(51)(52)(53)(54).…”

Section: Mutagenesis Analysis Of Sortilin Reveals Two Cytoplasmic Motmentioning

confidence: 99%

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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Identification of a novel conserved sorting motif required for retromer-mediated endosome-to-TGN retrieval

Cited by 228 publications

References 36 publications

Sorting of the Yeast Vacuolar-type, Proton-translocating ATPase Enzyme Complex (V-ATPase)

Sorting of the Yeast Vacuolar-type, Proton-translocating ATPase Enzyme Complex (V-ATPase)

Clathrin-mediated endocytosis is inhibited during mitosis

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

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