TORC2-Dependent Ypk1-Mediated Phosphorylation of Lam2/Ltc4 Disrupts Its Association with the β-Propeller Protein Laf1 at Endoplasmic Reticulum-Plasma Membrane Contact Sites in the Yeast Saccharomyces cerevisiae

Topolska, Magdalena; Roelants, Françoise M.; Edward, P; Thorner, Jeremy

doi:10.3390/biom10121598

Cited by 9 publications

(12 citation statements)

References 66 publications

(73 reference statements)

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“…Given our findings [ 211 ] that Ypk1-mediated phosphorylation of Lam2 and Lam4 inhibits their function in retrograde sterol transport, we sought to understand the mechanism of this negative regulation. We found [ 222 ], in agreement with a prior study [ 58 ] that, at ER-plasma membrane contact sites, Lam2 and Lam4 associate with two paralogous β-propeller (WD40 repeat) proteins Laf1/Ymr102c and Dgr2/Ykl121w, one of which was detected as a sterol-binding protein [ 223 ]. Using fluorescent tags, we showed that Lam2 and Lam4 remain at ER-plasma membrane contact sites when Laf1 and Dgr2 are absent, whereas neither Laf1 nor Dgr2 remain at ER-plasma membrane contact sites when Lam2 and Lam4 are absent [ 222 ].…”

Section: Functions Of Ypk1supporting

confidence: 91%

“…We found [ 222 ], in agreement with a prior study [ 58 ] that, at ER-plasma membrane contact sites, Lam2 and Lam4 associate with two paralogous β-propeller (WD40 repeat) proteins Laf1/Ymr102c and Dgr2/Ykl121w, one of which was detected as a sterol-binding protein [ 223 ]. Using fluorescent tags, we showed that Lam2 and Lam4 remain at ER-plasma membrane contact sites when Laf1 and Dgr2 are absent, whereas neither Laf1 nor Dgr2 remain at ER-plasma membrane contact sites when Lam2 and Lam4 are absent [ 222 ]. Furthermore, loss of Laf1 (but not Dgr2) impeded retrograde ergosterol transport, and a laf1Δ mutation did not exacerbate the transport defect of lam2Δ lam4Δ cells, indicating a shared function.…”

Section: Functions Of Ypk1supporting

confidence: 91%

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TOR complex 2 is a master regulator of plasma membrane homeostasis

Thorner

2022

Biochemical Journal

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As first demonstrated in budding yeast (Saccharomyces cerevisiae), all eukaryotic cells contain two, distinct multi-component protein kinase complexes that each harbor the TOR (Target Of Rapamycin) polypeptide as the catalytic subunit. These ensembles, dubbed TORC1 and TORC2, function as universal, centrally important sensors, integrators, and controllers of eukaryotic cell growth and homeostasis. TORC1, activated on the cytosolic surface of the lysosome (or, in yeast, on the cytosolic surface of the vacuole), has emerged as a primary nutrient sensor that promotes cellular biosynthesis and suppresses autophagy. TORC2, located primarily at the plasma membrane, plays a major role in maintaining the proper levels and bilayer distribution of all plasma membrane components (sphingolipids, glycerophospholipids, sterols, and integral membrane proteins). This article surveys what we have learned about signaling via the TORC2 complex, largely through studies conducted in S. cerevisiae. In this yeast, conditions that challenge plasma membrane integrity can, depending on the nature of the stress, stimulate or inhibit TORC2, resulting in, respectively, up-regulation or down-regulation of the phosphorylation and thus the activity of its essential downstream effector the AGC family protein kinase Ypk1. Through the ensuing effect on the efficiency with which Ypk1 phosphorylates multiple substrates that control diverse processes, membrane homeostasis is maintained. Thus, the major focus here is on TORC2, Ypk1, and the multifarious targets of Ypk1 and how the functions of these substrates are regulated by their Ypk1-mediated phosphorylation, with emphasis on recent advances in our understanding of these processes.

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Section: Functions Of Ypk1supporting

confidence: 91%

Section: Functions Of Ypk1supporting

confidence: 91%

TOR complex 2 is a master regulator of plasma membrane homeostasis

Thorner

2022

Biochemical Journal

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“…Loss of these four retained tethers reduces the amount of cortically retained ER at anaphase II but does not completely prevent ER retention, suggesting that additional tethers and/or alternative mechanisms ensure cortical ER tethering in this context. In addition to the six defined tethers, other proteins have been observed to localize to ER-PM contact sites, and some have been proposed as active ER-PM tethering proteins ( Petkovic et al, 2014 ; Topolska et al, 2020 ). Study of these additional factors will be important to further interrogate the molecular basis of cortical ER retention during meiosis and its role in ensuring gamete health.…”

Section: Discussionmentioning

confidence: 99%

Programmed cortical ER collapse drives selective ER degradation and inheritance in yeast meiosis

Otto

Cheunkarndee

Leslie

et al. 2021

Journal of Cell Biology

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The endoplasmic reticulum (ER) carries out essential and conserved cellular functions, which depend on the maintenance of its structure and subcellular distribution. Here, we report developmentally regulated changes in ER morphology and composition during budding yeast meiosis, a conserved differentiation program that gives rise to gametes. A subset of the cortical ER collapses away from the plasma membrane at anaphase II, thus separating into a spatially distinct compartment. This programmed collapse depends on the transcription factor Ndt80, conserved ER membrane structuring proteins Lnp1 and reticulons, and the actin cytoskeleton. A subset of ER is retained at the mother cell plasma membrane and excluded from gamete cells via the action of ER–plasma membrane tethering proteins. ER remodeling is coupled to ER degradation by selective autophagy, which relies on ER collapse and is regulated by timed expression of the autophagy receptor Atg40. Thus, developmentally programmed changes in ER morphology determine the selective degradation or inheritance of ER subdomains by gametes.

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“…However, deletion of all six tethers eliminates almost all cortical ER even in non-meiotic cells, complicating our ability to assess meiotic cortical ER retention in this genotype. In addition to these six tethers, other proteins have been observed to localize to ER-PM contact sites, and some have been proposed as active ER-PM tethering proteins (Petkovic et al, 2014; Topolska et al, 2020). Study of these additional factors will be important to further interrogate the molecular basis of cortical ER retention during meiosis and its role in ensuring gamete health.…”

Section: Discussionmentioning

confidence: 99%

Programmed ER fragmentation drives selective ER inheritance and degradation in budding yeast meiosis

Gm¹,

Cheunkarndee²,

Jm³

et al. 2021

Preprint

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The endoplasmic reticulum (ER) is a membrane-bound organelle with diverse, essential functions that rely on the maintenance of membrane shape and distribution within cells. ER structure and function are remodeled in response to changes in cellular demand, such as the presence of external stressors or the onset of cell differentiation, but mechanisms controlling ER remodeling during cell differentiation are not well understood. Here, we describe a series of developmentally regulated changes in ER morphology and composition during budding yeast meiosis, a conserved differentiation program that gives rise to gametes. During meiosis, the cortical ER undergoes fragmentation before collapsing away from the plasma membrane at anaphase II. This programmed collapse depends on the meiotic transcription factor Ndt80, conserved ER membrane structuring proteins Lnp1 and reticulons, and the actin cytoskeleton. A subset of ER is retained at the mother cell plasma membrane and excluded from gamete cells via the action of ER-plasma membrane tethering proteins. ER remodeling is coupled to ER degradation by selective autophagy, which is regulated by the developmentally timed expression of the autophagy receptor Atg40. Autophagy relies on ER collapse, as artificially targeting ER proteins to the cortically retained ER pool prevents their degradation. Thus, developmentally programmed changes in ER morphology determine the selective degradation or inheritance of ER subdomains by gametes.

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TORC2-Dependent Ypk1-Mediated Phosphorylation of Lam2/Ltc4 Disrupts Its Association with the β-Propeller Protein Laf1 at Endoplasmic Reticulum-Plasma Membrane Contact Sites in the Yeast Saccharomyces cerevisiae

Cited by 9 publications

References 66 publications

TOR complex 2 is a master regulator of plasma membrane homeostasis

TOR complex 2 is a master regulator of plasma membrane homeostasis

Programmed cortical ER collapse drives selective ER degradation and inheritance in yeast meiosis

Programmed ER fragmentation drives selective ER inheritance and degradation in budding yeast meiosis

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