Lipid raft involvement in yeast cell growth and death

Abstract

The notion that cellular membranes contain distinct microdomains, acting as scaffolds for signal transduction processes, has gained considerable momentum. In particular, a class of such domains that is rich in sphingolipids and cholesterol, termed as lipid rafts, is thought to compartmentalize the plasma membrane, and to have important roles in survival and cell death signaling in mammalian cells. Likewise, yeast lipid rafts are membrane domains enriched in sphingolipids and ergosterol, the yeast counterpart of mammalian cholesterol. Sterol-rich membrane domains have been identified in several fungal species, including the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe as well as the pathogens Candida albicans and Cryptococcus neoformans. Yeast rafts have been mainly involved in membrane trafficking, but increasing evidence implicates rafts in a wide range of additional cellular processes. Yeast lipid rafts house biologically important proteins involved in the proper function of yeast, such as proteins that control Na+, K+, and pH homeostasis, which influence many cellular processes, including cell growth and death. Membrane raft constituents affect drug susceptibility, and drugs interacting with sterols alter raft composition and membrane integrity, leading to yeast cell death. Because of the genetic tractability of yeast, analysis of yeast rafts could be an excellent model to approach unanswered questions of mammalian raft biology, and to understand the role of lipid rafts in the regulation of cell death and survival in human cells. A better insight in raft biology might lead to envisage new raft-mediated approaches to the treatment of human diseases where regulation of cell death and survival is critical, such as cancer and neurodegenerative diseases.

TORC2 and eisosomes are spatially interdependent, requiring optimal level of phosphatidylinositol 4, 5-bisphosphate for their integrity

“…An interconnection between microdomain proteins and sphingolipids has been well documented (Aguilar et al 2010;Dickson 2010;Mollinedo 2012;Niles et al 2014). Ergosterol, the yeast counterpart of mammalian cholesterol, localizes to the MCC (Grossmann et al 2007).…”

Med15B Regulates Acid Stress Response and Tolerance in Candida glabrata by Altering Membrane Lipid Composition

“…These include (i) increasing the content of long-chain fatty acids and UFAs, which leads to greater membrane fluidity and integrity (47,48); (ii) augmenting sterol content, which has an effect on membrane fluidity, increasing its thickness and sturdiness (49); and (iii) enhancing H ϩ -ATPase activity, which promotes proton efflux (35). Changes in the lipid composition of the med15BΔ strain might affect the activity of membrane proteins, which are essential for barrier function (50,51). The transcription factor Crz1 was shown to function in low-pH tolerance in C. glabrata (33).…”

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

“…Membrane nanodomains named lipid rafts, enriched in sterols and sphingolipids have been found to play a major role for the correct functioning of several cell survival signaling pathways Simons & Toomre, 2000) as well as of transporters and ion channels (Best & Kamp, 2012;Gueguinou, et al, 2014;Mollinedo, 2012;Pani & Singh, 2009;Rosenhouse-Dantsker, et al, 2012), including SK3 channel . In addition, lipid rafts have also been found to mediate death receptor signaling favoring the triggering of apoptosis (Gajate, et al, 2004;Gajate & Mollinedo, 2015b;.…”