Lateral plasma membrane compartmentalization links protein function and turnover

Biological membranes organize their proteins and lipids into nano‐ and microscale patterns. In the yeast plasma membrane (PM), constituents segregate into a large number of distinct domains. However, whether and how this intricate patchwork contributes to biological functions at the PM is still poor...

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Bibliographic Details
Published in:	The EMBO journal Vol. 37; no. 16
Main Authors:	Busto, Jon V, Elting, Annegret, Haase, Daniel, Spira, Felix, Kuhlman, Julian, Schäfer‐Herte, Marco, Wedlich‐Söldner, Roland
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 15-08-2018 Blackwell Publishing Ltd John Wiley and Sons Inc
Subjects:	amino acid permease Amino acids Biodegradation Biological membranes Cell Membrane - genetics Cell Membrane - metabolism Clustering EMBO20 EMBO31 endocytosis lateral membrane segregation Lipids Localization Mechanistic Target of Rapamycin Complex 2 - genetics Mechanistic Target of Rapamycin Complex 2 - metabolism Membrane proteins Methionine Nutrient availability patchwork membrane Permease plasma membrane Protein turnover Proteins Proteins - genetics Proteins - metabolism Relocation Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Signaling Sphingolipids Substrates Transport Ubiquitination Yeast Yeasts amino acid permease endocytosis patchwork membrane lateral membrane segregation plasma membrane
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Summary:	Biological membranes organize their proteins and lipids into nano‐ and microscale patterns. In the yeast plasma membrane (PM), constituents segregate into a large number of distinct domains. However, whether and how this intricate patchwork contributes to biological functions at the PM is still poorly understood. Here, we reveal an elaborate interplay between PM compartmentalization, physiological function, and endocytic turnover. Using the methionine permease Mup1 as model system, we demonstrate that this transporter segregates into PM clusters. Clustering requires sphingolipids, the tetraspanner protein Nce102, and signaling through TORC2. Importantly, we show that during substrate transport, a simple conformational change in Mup1 mediates rapid relocation into a unique disperse network at the PM. Clustered Mup1 is protected from turnover, whereas relocated Mup1 actively recruits the endocytic machinery thereby initiating its own turnover. Our findings suggest that lateral compartmentalization provides an important regulatory link between function and turnover of PM proteins. Synopsis Lateral segregation of a yeast amino acid permease, Mup1, controls its transport, function and endocytic turnover, providing an important level of regulation in the response of cells to nutrient availability. Lateral membrane segregation determines function and turnover of yeast amino acid permease Mup1. Protein clustering prevents Mup1 ubiquitination and endocytic degradation. Clustering requires sphingolipids, tetraspanners and TORC2 signaling. Conformational changes induced by substrate transport affect Mup1 localization in the membrane. Graphical Abstract Analyses on a yeast membrane permease Mup1 identify protein clustering in membrane domains as a regulatory mechanism.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 See also https://doi.org/10.15252/embj.2018100144 (August 2018) These authors contributed equally to this work
ISSN:	0261-4189 1460-2075
DOI:	10.15252/embj.201899473