Grd19/Snx3p functions as a cargo-specific adapter for retromer-dependent endocytic recycling

Strochlic, Todd I.; Setty, Thanuja Gangi; Sitaram, Anand; Burd, Christopher G.

doi:10.1083/jcb.200609161

Cited by 160 publications

(212 citation statements)

References 66 publications

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“…The retromer complex and the sorting nexin Snx3 function together in an endocytic recycling pathway to maintain the Fet3-Ftr1 high-affinity iron transporter at the plasma membrane at steady state when cells are starved for iron (Strochlic et al, 2007). Snx3 functions as a cargo-specific adapter in this pathway, binding both to a recycling signal in Ftr1 and to the retromer complex.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Vps26p, Vps29, and Vps35 comprise the cargo-recognition subcomplex of retromer, and the structure of the Vps29-Vps35 interface has recently been solved (Hierro et al, 2007). We and others have shown that another sorting nexin, Snx3/Grd19, associates with retromer and is necessary for retromer-dependent trafficking of a subset of retrograde cargo (Hettema et al, 2003;Restrepo et al, 2007;Strochlic et al, 2007).The fate of protein cargo within the endosomal system arises from the interplay of the cargo-sorting machineries of the retrograde and degradative pathways. Importantly, sorting of some proteins into the recycling versus degradative pathway is regulated such that signaling induces a switch from one pathway to the other.…”

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confidence: 99%

“…When cells are starved for iron, Fet3-Ftr1 is unusually stable because it is maintained at the plasma membrane due to retromer-dependent endocytic recycling (Strochlic et al, 2007). However, when cells are exposed to a high concentration of free iron in the culture medium, endocytosed Fet3-Ftr1 is transported to the vacuole and degraded (Felice et al, 2005).In a prior study, we showed that the sorting nexin, Snx3, directly recognizes a cytosolic signal in Ftr1 that is required for retromer-mediated retrograde transport (Strochlic et al, 2007). Snx3 and retromer physically associate, and they cooperate to prevent vacuolar degradation of Fet3-Ftr1 when cells are starved for iron.…”

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confidence: 99%

“…This form of Fet3 also contained a 3xHA epitope tag added to the C-terminus. All mutant loci were amplified by PCR and sequenced to ensure that only the desired mutations were present.To induce iron starvation, cells were grown to OD 600 Ϸ1.0 in synthetic media containing 50 M of the iron chelator bathophenanthrolinedisulfonic acid (BPS), as previously described (Strochlic et al, 2007). For iron-induced down-regulation assays (i.e., iron shock), late log-phase cells were washed once with water and once with synthetic medium and were then resuspended in synthetic medium containing 1 mM sodium ascorbate and 500 M ferric ammonium sulfate and incubated at 30°C.…”

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confidence: 99%

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Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome

Strochlic

Schmiedekamp

Lee

et al. 2008

MBoC

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Endocytosed proteins are either delivered to the lysosome to be degraded or are exported from the endosomal system and delivered to other organelles. Sorting of the Saccharomyces cerevisiae reductive iron transporter, composed of the Fet3 and Ftr1 proteins, in the endosomal system is regulated by available iron; in iron-starved cells, Fet3-Ftr1 is sorted by Snx3/Grd19 and retromer into a recycling pathway that delivers it back to the plasma membrane, but when starved cells are exposed to iron, Fet3-Ftr1 is targeted to the lysosome-like vacuole and is degraded. We report that iron-induced endocytosis of Fet3-Ftr1 is independent of Fet3-Ftr1 ubiquitylation, and after endocytosis, degradation of Fet3-Ftr1 is mediated by the multivesicular body (MVB) sorting pathway. In mutant cells lacking any component of the ESCRT protein-dependent MVB sorting machinery, the Rsp5 ubiquitin ligase, or in wild-type cells expressing Fet3-Ftr1 lacking cytosolic lysyl ubiquitin acceptor sites, Fet3-Ftr1 is constitutively sorted into the recycling pathway independent of iron status. In the presence and absence of iron, Fet3-Ftr1 transits an endosomal compartment where a subunit of the MVB sorting receptor (Vps27), Snx3/Grd19, and retromer proteins colocalize. We propose that this endosome is where Rsp5 ubiquitylates Fet3-Ftr1 and where the recycling and degradative pathways diverge. INTRODUCTIONThe endocytic pathway is initiated with the internalization of protein and lipid cargo from the plasma membrane. After endocytosis, internalized molecules transit through the endosomal system, a network of interconnected organelles that process and sort cargo molecules back to the plasma membrane, to other organelles, or to lysosomes for degradation. In mammalian cells, early endosomes are pleiomorphic organelles composed of vacuolar domains that contain lumenal vesicles and tubular domains that lead into and emanate from the vacuolar portion. This distinct architecture has functional significance. The tubular elements of the organelle are regions where the majority of internalized plasma membrane proteins and lipids are exported and recycled from the endosomal system via bulk flow and cargo-specific processes (Mayor et al., 1993;Maxfield and McGraw, 2004;Bonifacino and Rojas, 2006). Cargo proteins that are not exported are delivered to lysosomes and many of these are degraded. This occurs via an active, signal-mediated event in which these proteins are targeted to the vacuolar region of the endosome where they are incorporated into vesicles that bud from the limiting membrane into the lumen of the organelle (Piper and Katzmann, 2007). During endosome maturation lumenal vesicles accrue until fusion of the late endosome with the lysosome results in degradation of these vesicles and their contents. A central sorting function of the endosomal system is thus to segregate cargo to be exported from the endosome from cargo to be degraded via lysosomal proteolysis.The core components of the recycling (retrograde) and degradative sorting pathways have be...

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome

Strochlic

Schmiedekamp

Lee

et al. 2008

MBoC

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Back From the Brink: Retrieval of Membrane Proteins From Terminal Compartments

Seaman

2019

BioEssays

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Contact : mnjs100@cam.ac.uk, 44-1223-763225. SubtitleUnexpected pathways for membrane protein retrieval from vacuoles and endolysosomes. SummaryIt has long been believed that membrane proteins present in degradative compartments such as endolysosomes or vacuoles would be destined for destruction. Now however, it appears that mechanisms and machinery exist in simple eukaryotes such as yeast and more complex organisms such as mammals that can rescue potentially 'doomed' membrane proteins by retrieving them from these 'late' compartments and recycling them back to the Golgi complex. In yeast, a sorting nexin dimer containing Snx4p can recognise and retrieve the Atg27p membrane protein whilst in mammals, the AP5 complex (with SPG11 and SPG15) directs the recycling of Golgi-localised proteins along with the cation-independent mannose 6-phosphate receptor (CIMPR). Although the respective machinery is different, there is much commonality between yeast and mammals regarding the mechanisms of retrieval and the physiological importance of these late recycling pathways.

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Myo1 localizes to phagosomes, some of which traffic to the nucleus in a Myo1‐dependent manner in Tetrahymena thermophila

Hosein

Gavin

2007

Cell Motil. Cytoskeleton

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Myo1 is one of 13 myosins in Tetrahymena thermophila. Initially, twelve of the myosins in Tetrahymena were assigned to Class XX in the myosin superfamily but recently re-assigned to a subclass within Class XIV. In a previous study, we reported that genomic knockout of MYO1 affected phagocytosis and macronuclear amitosis. These two phenotypes have appeared disparate because a possible mechanism linking phagocytosis and amitosis was unknown. In the present study, Myo1 localization was investigated in order to further link machinery for phagocytosis and amitosis. Antibodies directed against the Myo1 motor domain detected an immunospecific polypeptide at 175-180 kDa on immunoblots of wild-type proteins. The 175-180 kDa polypeptide was not detected on immunoblots of proteins from the knockout strain. For immunofluorescence microscopy, cells were allowed to internalize fluorescent beads as markers for phagosomes. In wild-type cells, anti-Myo1 and anti-actin antibodies co-localized to the periphery of phagosomes and the macronucleus. In the MYO1-knockout strain only background fluorescence was observed with anti-Myo1 antibody. Confocal x-z series through macronuclei revealed fluorescent beads within the nucleoplasm. Statistical analysis showed a significant difference between the mean distributions of fluorescent beads in the nucleoplasm of wild-type and MYO1-knockout cells. A fluorescent dye was used to label plasma membrane in living cells. Dye-labeled vacuoles trafficked to the macronucleus. Trafficking of phagosomes to the macronucleus in a myosin-dependent manner is a novel finding and a possible mechanism for targeting myosin and actin to the nucleus.

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Grd19/Snx3p functions as a cargo-specific adapter for retromer-dependent endocytic recycling

Cited by 160 publications

References 66 publications

Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome

Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome

Back From the Brink: Retrieval of Membrane Proteins From Terminal Compartments

Myo1 localizes to phagosomes, some of which traffic to the nucleus in a Myo1‐dependent manner in Tetrahymena thermophila

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