Role of MCC/Eisosome in Fungal Lipid Homeostasis

Abstract

One of the best characterized fungal membrane microdomains is the MCC/eisosome. The MCC (membrane compartment of Can1) is an evolutionarily conserved ergosterol-rich plasma membrane domain. It is stabilized on its cytosolic face by the eisosome, a hemitubular protein complex composed of Bin/Amphiphysin/Rvs (BAR) domain-containing Pil1 and Lsp1. These two proteins bind directly to phosphatidylinositol 4,5-bisphosphate and promote the typical furrow-like shape of the microdomain, with highly curved edges and bottom. While some proteins display stable localization in the MCC/eisosome, others enter or leave it under particular conditions, such as misbalance in membrane lipid composition, changes in membrane tension, or availability of specific nutrients. These findings reveal that the MCC/eisosome, a plasma membrane microdomain with distinct morphology and lipid composition, acts as a multifaceted regulator of various cellular processes including metabolic pathways, cellular morphogenesis, signalling cascades, and mRNA decay. In this minireview, we focus on the MCC/eisosome's proposed role in the regulation of lipid metabolism. While the molecular mechanisms of the MCC/eisosome function are not completely understood, the idea of intracellular processes being regulated at the plasma membrane, the foremost barrier exposed to environmental challenges, is truly exciting.

Keywords: MCC; eisosome; ergosterol; lipids; microdomain; phosphoinositides; regulation; sphingolipids.

Figure 1

Distribution of membrane compartment of Can1 (MCC) markers in selected knockout strains. Distributions of Can1-GFP, Sur7-GFP, and filipin-stained sterols were monitored in the library of single gene deletion strains. Examples of detected phenotypes (classification of phenotypes: wild type [WT]—like, −; weak, +; medium, ++; strong, +++) on tangential confocal sections (Can1 and Sur7) or wide-field images (filipin; transversal sections) are presented. Figure adapted from [6] (©2008 Grossmann et al. Originally published in Journal of Cell Biology. https://doi.org/10.1083/jcb.200806035).

Figure 2

Interplay of MCC/eisosomes and sphingolipid biosynthesis. (a) The MCC/eisosome is fully assembled under basal, non-stress conditions. (b) MCC/eisosome disassembles following depletion of sphingolipids and/or mechanical stretching of the plasma membrane, resulting in activation of TORC2 and in turn SPT, catalysing the first step of sphingolipid biosynthesis. Short descriptions of proteins involved in this model are listed in Table 1. Used abbreviations: ER—endoplasmic reticulum; IPC—inositol phosphoceramide; LCBs—long chain bases; MCC—membrane compartment of Can1; M(IP)₂C—mannose-(inositol-P)₂-ceramide; MIPC—mannosyl-inositol phosphoceramide; Pal-CoA—palmitoyl coenzyme-A; PI—phosphatidylinositol; PI(4,5)P₂—phosphatidylinositol 4,5-bisphosphate; PI(4)P—phosphatidylinositol 4-phosphate; PM—plasma membrane; SPT—serine palmitoyltransferase; TORC2—Tor Complex 2.