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Plasma membrane microdomains regulate turnover of transport proteins in yeast.

Grossmann G, Malinsky J, Stahlschmidt W, Loibl M, Weig-Meckl I, Frommer WB, Opekarová M, Tanner W - J. Cell Biol. (2008)

Bottom Line: Deletion of Pil1, a component of eisosomes, or of Nce102, an integral membrane protein of MCC, results in the dissipation of all MCC markers.These deletion mutants also show accelerated endocytosis of MCC-resident permeases Can1 and Fur4.Addition of arginine to wild-type cells leads to a similar redistribution and increased turnover of Can1.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cell Biology and Plant Physiology, University of Regensburg, 93053 Regensburg, Germany.

ABSTRACT
In this study, we investigate whether the stable segregation of proteins and lipids within the yeast plasma membrane serves a particular biological function. We show that 21 proteins cluster within or associate with the ergosterol-rich membrane compartment of Can1 (MCC). However, proteins of the endocytic machinery are excluded from MCC. In a screen, we identified 28 genes affecting MCC appearance and found that genes involved in lipid biosynthesis and vesicle transport are significantly overrepresented. Deletion of Pil1, a component of eisosomes, or of Nce102, an integral membrane protein of MCC, results in the dissipation of all MCC markers. These deletion mutants also show accelerated endocytosis of MCC-resident permeases Can1 and Fur4. Our data suggest that release from MCC makes these proteins accessible to the endocytic machinery. Addition of arginine to wild-type cells leads to a similar redistribution and increased turnover of Can1. Thus, MCC represents a protective area within the plasma membrane to control turnover of transport proteins.

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Model of spatially confined protein turnover. In the presence of low substrate concentrations, specific transporters are concentrated in MCC and protected against internalization (A). After the excess of substrate is supplied (B), the transporters are released from the MCC patches to the surrounding membrane (C) and subjected to endocytosis (D).
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fig10: Model of spatially confined protein turnover. In the presence of low substrate concentrations, specific transporters are concentrated in MCC and protected against internalization (A). After the excess of substrate is supplied (B), the transporters are released from the MCC patches to the surrounding membrane (C) and subjected to endocytosis (D).

Mentions: So far, we can only speculate on the molecular mechanism of the MCC shelter function. Because Pil1 down-regulates the Pkc1–mitogen-activated protein and Ypk1 pathways also involved in endocytosis (Zhang et al., 2004), it is conceivable that endocytosis is inhibited at places of Pil1 accumulation. In other words, Pil1 clustering underneath MCC patches directs the endocytic activity outside this specialized membrane area. As follows from our results, Nce102 anchors Can1, Fur4, and others within this area and thus protects them from internalization. The anchoring interaction seems to be mediated by Coulombic forces, as Can1 but not Nce102 (Fig. 6) is released from the MCC patches after membrane depolarization. With respect to endocytosis, two functionally distinct compartments coexist within the plasma membrane: MCC patches with the combined protecting potential of Nce102 and Pil1 and a remaining unprotected area (Fig. 10). This phenomenon can serve as an example of a spatially confined regulatory mechanism.


Plasma membrane microdomains regulate turnover of transport proteins in yeast.

Grossmann G, Malinsky J, Stahlschmidt W, Loibl M, Weig-Meckl I, Frommer WB, Opekarová M, Tanner W - J. Cell Biol. (2008)

Model of spatially confined protein turnover. In the presence of low substrate concentrations, specific transporters are concentrated in MCC and protected against internalization (A). After the excess of substrate is supplied (B), the transporters are released from the MCC patches to the surrounding membrane (C) and subjected to endocytosis (D).
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2600745&req=5

fig10: Model of spatially confined protein turnover. In the presence of low substrate concentrations, specific transporters are concentrated in MCC and protected against internalization (A). After the excess of substrate is supplied (B), the transporters are released from the MCC patches to the surrounding membrane (C) and subjected to endocytosis (D).
Mentions: So far, we can only speculate on the molecular mechanism of the MCC shelter function. Because Pil1 down-regulates the Pkc1–mitogen-activated protein and Ypk1 pathways also involved in endocytosis (Zhang et al., 2004), it is conceivable that endocytosis is inhibited at places of Pil1 accumulation. In other words, Pil1 clustering underneath MCC patches directs the endocytic activity outside this specialized membrane area. As follows from our results, Nce102 anchors Can1, Fur4, and others within this area and thus protects them from internalization. The anchoring interaction seems to be mediated by Coulombic forces, as Can1 but not Nce102 (Fig. 6) is released from the MCC patches after membrane depolarization. With respect to endocytosis, two functionally distinct compartments coexist within the plasma membrane: MCC patches with the combined protecting potential of Nce102 and Pil1 and a remaining unprotected area (Fig. 10). This phenomenon can serve as an example of a spatially confined regulatory mechanism.

Bottom Line: Deletion of Pil1, a component of eisosomes, or of Nce102, an integral membrane protein of MCC, results in the dissipation of all MCC markers.These deletion mutants also show accelerated endocytosis of MCC-resident permeases Can1 and Fur4.Addition of arginine to wild-type cells leads to a similar redistribution and increased turnover of Can1.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cell Biology and Plant Physiology, University of Regensburg, 93053 Regensburg, Germany.

ABSTRACT
In this study, we investigate whether the stable segregation of proteins and lipids within the yeast plasma membrane serves a particular biological function. We show that 21 proteins cluster within or associate with the ergosterol-rich membrane compartment of Can1 (MCC). However, proteins of the endocytic machinery are excluded from MCC. In a screen, we identified 28 genes affecting MCC appearance and found that genes involved in lipid biosynthesis and vesicle transport are significantly overrepresented. Deletion of Pil1, a component of eisosomes, or of Nce102, an integral membrane protein of MCC, results in the dissipation of all MCC markers. These deletion mutants also show accelerated endocytosis of MCC-resident permeases Can1 and Fur4. Our data suggest that release from MCC makes these proteins accessible to the endocytic machinery. Addition of arginine to wild-type cells leads to a similar redistribution and increased turnover of Can1. Thus, MCC represents a protective area within the plasma membrane to control turnover of transport proteins.

Show MeSH
Related in: MedlinePlus