8.A.148.  The Plasma Membrane Organizing Center, Eisosome (Eisosome) Family 

Eisosomes are protein-organized domains in the plasma membranes of fungi and algae (Douglas and Konopka 2014). Eisosomes are also called 'membrane compartment occupied by Can1' (MCC).  Can1 is an arginine transporter (TC# 2.A.3.10.4; S. cerevisiae) and TC# 2.A.3.10.20; C. albicans). The fungal plasma membrane is organized into specialized domains that vary in size, stability, and composition. Membrane compartment of eisosome domains were first discovered in Saccharomyces cerevisiae. They represent a novel type of membrane domain that is important for plasma membrane organization, sphingolipid homeostasis, and cell wall morphogenesis. The MCC regions are stable punctate patches that correspond to furrows in the plasma membrane, about 300 nm long and 50 nm deep. These domains contain integral membrane proteins, including the tetraspan proteins Sur7 and Nce2. The eisosome includes proteins peripherally associated with the cytoplasmic side of the MCC, including the Bin/amphiphysin/Rvs-domain proteins, Pil1 and Lsp1, which assemble into filaments that curve the membrane to form the furrows. By comparing MCC/eisosome domains in diverse fungi, researchers are identifying common features that further our understanding of their unique biogenesis, structure, and function (Douglas and Konopka 2014).

EIS1 is required for normal formation of eisosomes, large cytoplasmic protein assemblies that localize to specialized domains in/on plasma membranes and mark the sites of endocytosis (Aguilar et al. 2010). SEG1 is important for the biogenesis of eisosomes, specialized domains on the plasma membrane that cluster specific proteins at sites of membrane invaginations. It is required for efficient incorporation of the eisosomal component PIL1. PIL1 is a negative regulator of cell wall integrity (CWI) in unstressed cells, probably by inhibiting protein kinase PKH1/PHK2 activity and regulating their downstream CWI pathways, the PKC1-MAP kinase pathway and the protein kinase YPK1 pathway. Activity may be regulated by the transient increase of sphingolipid long chain bases during heat stress (Zhang et al. 2004). Together with Pil1, Lsp1 is a main component of eisosomes and forms filaments, structures at the cell periphery underneath the plasma membrane that mark the site of endocytosis. Lsp1 may be a negative regulator of CWI in unstressed cells, probably by inhibiting protein kinase PKH1/PHK2 activity and regulating their downstream CWI pathways. Activity may be regulated by the transient increase of sphingolipid long chain bases during heat stress (Zhang et al. 2004). Sur7 is a 4 TMS protein involved in sporulation and endocytosis, affecting the sphingolipid composition of the plasma membrane (Young et al. 2002). The eisosome contains many transport proteins such as Can1 and influences their activities.  Nce2 (Nce102) contains a MARVEL domain that regulates actin organization (Douglas et al. 2013).