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

Strochlic, Todd I., Setty, Thanuja Gangi, Sitaram, Anand, Burd, Christopher G.·2007·The Journal of Cell Biology
DOI 10.1083/jcb.200609161PMC PMC2064116
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Abstract

Amajor function of the endocytic system is the sorting of cargo to various organelles. Endocytic sorting of the yeast reductive iron transporter, which is composed of the Fet3 and Ftr1 proteins, is regulated by available iron. When iron is provided to iron-starved cells, Fet3p–Ftr1p is targeted to the lysosome-like vacuole and degraded. In contrast, when iron is not available, Fet3p–Ftr1p is maintained on the plasma membrane via an endocytic recycling pathway requiring the sorting nexin Grd19/Snx3p, the pentameric retromer complex, and the Ypt6p Golgi Rab GTPase module. A recycling signal in Ftr1p was identified and found to bind directly to Grd19/Snx3p. Retromer and Grd19/Snx3p partially colocalize to tubular endosomes, where they are physically associated. After export from the endosome, Fet3p–Ftr1p transits through the Golgi apparatus for resecretion. Thus, Grd19/Snx3p, functions as a cargo-specific adapter for the retromer complex, establishing a precedent for a mechanism by which sorting nexins expand the repertoire of retromer-dependent cargos.

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  • SNX3 directly binds to a subset of cargo containing the sequence motif [+/-]-x-∅-x-[L/M], with many of these cargoes trafficked through the retrograde endosome-to-TGN pathway.

    “SNX3 directly binds to a subset of cargo containing the poorly defined sequence motif [+/-]-x-∅-x-[L/M] (∅ -bulky aromatic residue) with many of these cargoes trafficked through the retrograde endosome-to-TGN pathway [25,30,66,67].”

    From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [30]

    The Results section reports that Grd19p, the yeast SNX3 homologue, directly binds the Ftr1p recycling signal; the Discussion also identifies cargo sorted through the Grd19p–retromer pathway, including proteins retrieved to the Golgi. But the Discussion does not establish the claimed sequence motif. It says the signals appear diverse, a phenylalanine mutation did not affect Ftr1p recycling, and Grd19p probably recognizes structural features rather than a strict linear sequence. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The SNX3-Retromer assembly is essential for the sequence-dependent retrieval and recycling of cargoes.

    “An additional cargo adaptor complex essential for the sequence-dependent retrieval and recycling of cargoes is the sorting nexin-3 (SNX3)-Retromer assembly [25,30,66,67].”

    From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [30]

  • Retromer associates with accessory proteins and cargo adaptors including sorting nexins, the WASH complex, RAB GTPase regulators including TBC1D5 and ANKRD27/VARP, and RME8.

    “To function, Retromer associates with accessory proteins and cargo adaptors including sorting nexins (SNXs) [24][25][26][27][28][29][30][31][32][33][34], the WASH complex [35][36][37][38][39], RAB GTPase regulators including TBC1D5 and ANKRD27/VARP [40][41][42][43][44][45][46], and RME8 [47].”

    From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [30]

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Metadata

Authors
Strochlic, T. I., Setty, T. G., Sitaram, A., & Burd, C. G.
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2007-04-09
Volume
177
Issue
1
Pages
115-125
ISSN
  • 1540-8140
  • 0021-9525
DOI
10.1083/jcb.200609161
PMC
PMC2064116
Cited by
165
References
1
Language
en

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