Maintaining protein homeostasis: early and late endosomal dual recycling for the maintenance of intracellular pools of the plasma membrane protein Chs3

Arcones, Irene; Sacristán, Carlos; Roncero, César

doi:10.1091/mbc.e16-04-0239

Cited by 22 publications

(24 citation statements)

References 60 publications

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“…We used strains carrying mutations in different transport steps to examine the trafficking itineraries of Chs3 and variant forms of Chs7. Chs3 has sorting signals for binding AP‐1, retromer and exomer, and is retained intracellularly in exomer mutants by continuous AP‐1‐dependent cycling between Golgi and endosomes . In chs6∆ mutants, Chs7‐GFP was trapped in intracellular Golgi/endosomal compartments, but was sorted to the vacuole when the Chs3 interaction was abrogated by mutation of the Chs7 tail (Figure B).…”

Section: Resultsmentioning

confidence: 96%

“…Chs7 does not absolutely require Chs3 for its ER exit, yet strongly depends on its association with Chs3 for subsequent trafficking steps (Figure ). Exomer‐dependent transport of Chs7 was observed only when it was bound to Chs3, suggesting Chs7 relies on Chs3 to provide sorting signals that direct its own trafficking itinerary. When not stably associated with Chs3, Chs7 was largely transported to the vacuole via the late endosome/multi‐vesicular body (MVB).…”

Section: Discussionmentioning

confidence: 99%

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The chaperone Chs7 forms a stable complex with Chs3 and promotes its activity at the cell surface

Dharwada

Dalton

Bean

et al. 2018

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The polytopic yeast protein Chs3 (chitin synthase III) relies on a dedicated membrane-localized chaperone, Chs7, for its folding and expression at the cell surface. In the absence of Chs7, Chs3 forms high molecular weight aggregates and is retained in the endoplasmic reticulum (ER). Chs7 was reported to be an ER resident protein, but its role in Chs3 folding and transport was not well characterized. Here, we show that Chs7 itself exits the ER and localizes with Chs3 at the bud neck and intracellular compartments. We identified mutations in the Chs7 C-terminal cytosolic domain that do not affect its chaperone function, but cause it to dissociate from Chs3 at a post-ER transport step. Mutations that prevent the continued association of Chs7 with Chs3 do not block delivery of Chs3 to the cell surface, but dramatically reduce its catalytic activity. This suggests that Chs7 engages in functionally distinct interactions with Chs3 to first promote its folding and ER exit, and subsequently to regulate its activity at the plasma membrane.

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Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

The chaperone Chs7 forms a stable complex with Chs3 and promotes its activity at the cell surface

Dharwada

Dalton

Bean

et al. 2018

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“…S2F), likely reflecting separate pathways for degrading distinct pools of protein. For example, Chs3 is present on the vacuolar membrane where it is partially internalized and degraded (13) but also on the ER from where it might be delivered to the proteasome.…”

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confidence: 99%

A Systematic Protein Turnover Map for Decoding Protein Degradation

Christiano

Kabatnik

Mejhert

et al. 2020

Preprint

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One Sentence Summary: A systematic, global map of protein turnover for a large set of yeast mutants reveals scope and specificity of degradation pathways and identifies novel regulatory nodes for lipid metabolism. Protein degradation is mediated by an expansive and complex network of protein modification and degradation enzymes. Matching degradation enzymes with their targets and determining globally which proteins are degraded by the proteasome or lysosome/vacuole has been a major challenge. Further, an integrated view of protein degradation for cellular pathways has been lacking. Here we present a novel analytical platform that combines systematic gene deletions with quantitative measures of protein turnover to deconvolve protein degradation pathways for S. cerevisiae. The resulting turnover map (T-MAP) reveals target candidates of nearly all E2 and E3 ubiquitin ligases and identifies the primary degradation routes for most proteins. We further mined this T-MAP to identify new substrates of ER-associated Degradation (ERAD) involved in sterol biosynthesis and to uncover novel regulatory nodes for sphingolipid biosynthesis. The T-MAP approach should be broadly applicable to the study of other cellular processes and systems, including mammalian systems.

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“…In yeasts, which do not maintain polar growth and where the microtubule cytoskeleton is not critical for cargo traffic, AP-1 null mutants are viable, showing relatively moderate growth defects, which in some cases are associated with problematic traffic of specific cargoes, such as chitin synthase Chs3 (Valdivia et al 2002; Ma et al, 2009; Yu et al, 2013; Arcones et al, 2016). Yeast AP-1 null mutants also have minor defects in lipid PtdIns(3,5)P2-dependent processes and show reduced ability to traffic ubiquitylated cargoes to the vacuole lumen (Phelan et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…AP-1 was also shown to be responsible for retrograde transport from early endosomes in both yeast and mammalian cells, but also guiding recycling pathways from the endosome to the plasma membrane in yeast (Spang 2015). The undisputed essentiality of AP-1 and AP-2 in mammalians cells is however less obvious in simple unicellular eukaryotes, such as the yeasts Saccharomyces cerevisiae or Schizosaccharomyces pombe , where null mutants in the genes encoding AP subunits are viable, with only relatively minor growth or morphological defects (Meyer et al, 2000; Valdivia et al 2002; Ma et al, 2009; Yu et al, 2013; Arcones et al, 2016). In sharp contrast, the growth of AP-1 and AP-2 null mutants in the filamentous fungus Aspergillus nidulans is severally arrested after spore germination (Martzoukou et al, 2017 and results presented herein), reflecting blocks in essential cellular processes, probably similar to mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

The AP-1 complex is essential for fungal growth via its role in secretory vesicle polar sorting, endosomal recycling and cytoskeleton organization

Μαρτζούκου¹,

Diallinas²,

Amillis³

2018

Preprint

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The AP-1 complex is essential for membrane protein traffic via its role in the pinching-off and sorting of secretory vesicles from the trans-Golgi and/or endosomes. While its essentiality is undisputed in metazoa, its role in model simpler eukaryotes seems less clear. Here we dissect the role of AP-1 in the filamentous fungus Aspergillus nidulans and show that it is absolutely essential for growth due to its role in clathrin-dependent maintenance of polar traffic of specific membrane cargoes towards the apex of growing hyphae. We provide evidence that AP-1 is involved in both anterograde sorting of RabERab11-labeled secretory vesicles and RabA/BRab5- dependent endosome recycling. Additionally, AP-1 is shown to be critical for microtubule and septin organization, further rationalizing its essentiality in cells that face the challenge of cytoskeleton-dependent polarized cargo traffic. This work also opens a novel issue on how non-polar cargoes, such as transporters, are sorted to the eukaryotic plasma membrane.

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Maintaining protein homeostasis: early and late endosomal dual recycling for the maintenance of intracellular pools of the plasma membrane protein Chs3

Cited by 22 publications

References 60 publications

The chaperone Chs7 forms a stable complex with Chs3 and promotes its activity at the cell surface

The chaperone Chs7 forms a stable complex with Chs3 and promotes its activity at the cell surface

A Systematic Protein Turnover Map for Decoding Protein Degradation

The AP-1 complex is essential for fungal growth via its role in secretory vesicle polar sorting, endosomal recycling and cytoskeleton organization

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