The Sphingolipid Long-chain Base-Pkh1/2-Ypk1/2 Signaling Pathway Regulates Eisosome Assembly and Turnover

Luo, Guangzuo; Gruhler, Albrecht; Liu, Ying; Jensen, Ole N.; Dickson, Robert C.

doi:10.1074/jbc.m709972200

Cited by 107 publications

(166 citation statements)

References 42 publications

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“…Moreover, Pil1 and Lsp1 are differentially phosphorylated in re-sponse to an increase of long-chain bases, which are the precursors of sphingolipids, by Pkh1/2, two kinases that localize to eisosomes (Zhang et al, 2004;Walther et al, 2007;Luo et al, 2008). Perturbation of the Pil1 phosphorylation status affects Pil1 assembly into eisosomes: specifically, eisosomes disassemble if Pil1 is hyperphosphorylated, and more Pil1 assembles into eisosomes if Pil1 is hypophosphorylated.…”

Section: Discussionmentioning

confidence: 99%

Pil1 Controls Eisosome Biogenesis

Moreira

Walther

Aguilar

et al. 2009

MBoC

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The molecular composition of plasma membranes is constantly remodeled by endocytosis and exocytosis. Eisosomes are large cytoplasmic protein assemblies that localize to specialized domains on the yeast plasma membrane. They are of uniform size and immobile, and their disruption leads to large aberrant plasma membrane invaginations and endocytic defects. It is unknown how eisosomes are formed or inherited and what governs their size, distribution, and location. Here we show that eisosomes are formed de novo in the bud of dividing cells. They colonize newly formed membrane at a fixed density in a polarized wave proceeding from the bud neck to the bud tip and become anchored at the site of their formation. Pil1, one of the two main eisosome subunits, emerges as the central regulator of eisosome biogenesis that determines both size and location of eisosomes. Lowering Pil1 expression leads to normal-sized eisosomes at a reduced density, suggesting that eisosomes must be of a minimal size. Conversely, raising Pil1 expression leads to larger eisosomes at a fixed density, suggesting that under these conditions eisosome nucleation sites are limiting. Pil1 expression is regulated by the cell cycle, which synchronizes eisosome formation with plasma membrane growth. Our results establish a first framework of the molecular principles that define eisosome assembly and distribution.

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Section: Discussionmentioning

confidence: 99%

Pil1 Controls Eisosome Biogenesis

Moreira

Walther

Aguilar

et al. 2009

MBoC

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“…Long chain bases also regulate the phosphorylation of the primary components of the eisosome, Pil1 (phosphorylation inhibited by long chain bases) and Lsp1 (long chain bases stimulate phosphorylation). Appearance of membrane-associated eisosomes drastically changes in response to Pil1 hyper-or hypophosphorylation [16,34]. Whether and how these changes in eisosome morphology influence the furrow-like invaginations of the plasma membrane (MCC) is not yet known.…”

Section: Role Of Lipidsmentioning

confidence: 99%

The lateral compartmentation of the yeast plasma membrane

Malínský

Opekarová

Tanner

2010

Yeast

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The plasma membrane of Saccharomyces cerevisiae contains large microdomains enriched in ergosterol, which house at least nine integral proteins, including proton symporters. The domains adopt a characteristic structure of furrow-like invaginations typically seen in freeze-fracture pictures of fungal cells. Being stable for the time comparable with the cell cycle duration, they might be considered as fixed islands (rafts) in an otherwise fluid yeast plasma membrane. Rapidly moving endocytic marker proteins avoid the microdomains; the domain-accumulated proton symporters consequently show a reduced rate of substrate-induced endocytosis and turnover.

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“…One possibility is that striation variability may reflect a switch in "levels of engagement" between the eisosomal lipids and their underlying organizing systems. If this is the case, the variability could be a morphological reflection of (some of) the signal transduction properties attributed to eisosomes (19,20,22). Walther and colleagues (30,83) have suggested analogies between eisosomes and caveolae.…”

Section: Discussionmentioning

confidence: 99%

“…These observations were brought together by Strádalová et al (5), who showed that the membrane compartment occupied by Can1p (MCC) localized to the invaginations seen with freeze fracture EM, and by Karotki et al (6), who showed that Pil1p localizes to the cytoplasmic surfaces of these invaginations. Additional proteins also associate with these punctate domains, in some cases in a transient fashion (17), and the MCC component is reportedly enriched in ergosterol (18) and influenced by phosphoinositide (6,19,20) and sphingolipid (14,17,(21)(22)(23)(24) levels. Hence, the current yeast model (25,26) proposes that Pil1p and Lsp1p, which contain membrane curvatureinducing BAR domains (6,27,28), together with Seg1p (29,30), form a submembrane complex (6) reportedly influenced by Pil1p phosphorylation (25); this complex then either creates or associates with the MCC domains, presumably inducing an inward curvature.…”

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confidence: 99%

Eisosome Ultrastructure and Evolution in Fungi, Microalgae, and Lichens

et al. 2015

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Eisosomes are among the few remaining eukaryotic cellular differentations that lack a defined function(s). These trough-shaped invaginations of the plasma membrane have largely been studied in Saccharomyces cerevisiae, in which their associated proteins, including two BAR domain proteins, have been identified, and homologues have been found throughout the fungal radiation. Using quick-freeze deep-etch electron microscopy to generate high-resolution replicas of membrane fracture faces without the use of chemical fixation, we report that eisosomes are also present in a subset of red and green microalgae as well as in the cysts of the ciliate Euplotes. Eisosome assembly is closely correlated with both the presence and the nature of cell walls. Microalgal eisosomes vary extensively in topology and internal organization. Unlike fungi, their convex fracture faces can carry lineagespecific arrays of intramembranous particles, and their concave fracture faces usually display fine striations, also seen in fungi, that are pitched at lineage-specific angles and, in some cases, adopt a broad-banded patterning. The conserved genes that encode fungal eisosome-associated proteins are not found in sequenced algal genomes, but we identified genes encoding two algal lineage-specific families of predicted BAR domain proteins, called Green-BAR and Red-BAR, that are candidate eisosome organizers. We propose a model for eisosome formation wherein (i) positively charged recognition patches first establish contact with target membrane regions and (ii) a (partial) unwinding of the coiled-coil conformation of the BAR domains then allows interactions between the hydrophobic faces of their amphipathic helices and the lipid phase of the inner membrane leaflet, generating the striated patterns.

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The Sphingolipid Long-chain Base-Pkh1/2-Ypk1/2 Signaling Pathway Regulates Eisosome Assembly and Turnover

Cited by 107 publications

References 42 publications

Pil1 Controls Eisosome Biogenesis

Pil1 Controls Eisosome Biogenesis

The lateral compartmentation of the yeast plasma membrane

Eisosome Ultrastructure and Evolution in Fungi, Microalgae, and Lichens

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