Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells

Singh, Pushpendra; Ramachandran, Sreekumar; Zhu, Jin; Kim, Byoung Choul; Biswas, Debojyoti; Ha, Taekjip; Iglesias, Pablo A.; Li, Rong

doi:10.1091/mbc.e17-05-0335

Cited by 21 publications

(27 citation statements)

References 72 publications

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“…This does not appear to stem from unusual features of the proteins themselves, as similar proteins targeted to a yeast vacuolar membrane or a mammalian plasma membrane are far more mobile (D~0.1 µm 2 /s) [11]. Consistent with the cited studies, FRAP experiments on a variety of other membrane proteins detected very little recovery on 10 min timescales, in fission yeast as well as budding yeast [13][14][15]. Thus, it appears that yeast plasma membranes severely restrict diffusion of embedded proteins.…”

Section: Slow Diffusion Restricts Mobility In the Yeast Plasma Membranesupporting

confidence: 70%

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How Diffusion Impacts Cortical Protein Distribution in Yeasts

Moran¹,

Lew²

2020

Cells

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Proteins associated with the yeast plasma membrane often accumulate asymmetrically within the plane of the membrane. Asymmetric accumulation is thought to underlie diverse processes, including polarized growth, stress sensing, and aging. Here, we review our evolving understanding of how cells achieve asymmetric distributions of membrane proteins despite the anticipated dissipative effects of diffusion, and highlight recent findings suggesting that differential diffusion is exploited to create, rather than dissipate, asymmetry. We also highlight open questions about diffusion in yeast plasma membranes that remain unsolved.

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Section: Slow Diffusion Restricts Mobility In the Yeast Plasma Membranesupporting

confidence: 70%

“…Mutations that perturb the normal lipid composition of the plasma membrane can modestly increase protein diffusion [11,15]. Thus, an unusual lipid composition may increase membrane viscosity, hence slowing diffusion.…”

Section: Why Is Diffusion So Slow In the Yeast Plasma Membrane?mentioning

confidence: 99%

How Diffusion Impacts Cortical Protein Distribution in Yeasts

Moran¹,

Lew²

2020

Cells

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“…S7A and movie S9) ( 48 ). Using a microfluidic device to observe repeated budding cycles of single mother cells ( 49 ), we found that DUMP were asymmetrically retained in mother cells through most of the RLS ( Fig. 5B and movie S10).…”

Section: Resultsmentioning

confidence: 99%

Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix

et al. 2020

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Proteostasis declines with age, characterized by the accumulation of unfolded or damaged proteins. Recent studies suggest that proteins constituting pathological inclusions in neurodegenerative diseases also enter and accumulate in mitochondria. How unfolded proteins are managed within mitochondria remains unclear. Here, we found that excessive unfolded proteins in the mitochondrial matrix of yeast cells are consolidated into solid-phase inclusions, which we term deposits of unfolded mitochondrial proteins (DUMP). Formation of DUMP occurs in mitochondria near endoplasmic reticulum–mitochondria contact sites and is regulated by mitochondrial proteins controlling the production of cytidine 5′-diphosphate–diacylglycerol. DUMP formation is age dependent but accelerated by exogenous unfolded proteins. Many enzymes of the tricarboxylic acid cycle were enriched in DUMP. During yeast cell division, DUMP formation is necessary for asymmetric inheritance of damaged mitochondrial proteins between mother and daughter cells. We provide evidence that DUMP-like structures may be induced by excessive unfolded proteins in human cells.

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“…4 and SI Appendix, Fig. S2C) but also posttranslational protein modification (39) and the lipid composition of the PM (40). Additionally, a range of protein aggregates that are formed by cellular stress or aging tend to be retained in mother cells (7,41).…”

Section: Discussionmentioning

confidence: 99%

Distinct segregation patterns of yeast cell-peripheral proteins uncovered by a method for protein segregatome analysis

Sugiyama

Tanaka

2019

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

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Protein segregation contributes to various cellular processes such as polarization, differentiation, and aging. However, the difficulty in global determination of protein segregation hampers our understanding of its mechanisms and physiological roles. Here, by developing a quantitative proteomics technique, we globally monitored segregation of preexisting and newly synthesized proteins during cell division of budding yeast, and identified crucial domains that determine the segregation of cell-peripheral proteins. Remarkably, the proteomic and subsequent microscopic analyses demonstrated that the flow through the bud neck of the proteins that harbor both endoplasmic reticulum (ER) membrane-spanning and plasma membrane (PM)-binding domains is not restricted by the previously suggested ER membrane or PM diffusion barriers but by septin-mediated partitioning of the PM-associated ER (pmaER). Furthermore, the proteomic analysis revealed that although the PM-spanning t-SNARE Sso2 was retained in mother cells, its paralog Sso1 unexpectedly showed symmetric localization. We found that the transport of Sso1 to buds was required for enhancement of polarized cell growth and resistance to cell-wall stress. Taken together, these data resolve long-standing questions about septin-mediated compartmentalization of the cell periphery, and provide new mechanistic insights into the segregation of cell-periphery proteins and their cellular functions.

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Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells

Abstract: Asymmetrically dividing yeast cells segregate determinants of aging, and sphingolipids play a role in restricting the diffusion, and thus the mixing, of young and aged plasma membrane proteins.

Cited by 21 publications

References 72 publications

How Diffusion Impacts Cortical Protein Distribution in Yeasts

How Diffusion Impacts Cortical Protein Distribution in Yeasts

Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix

Distinct segregation patterns of yeast cell-peripheral proteins uncovered by a method for protein segregatome analysis

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