Abstract
The lipid raft hypothesis emerged as a need to explain the lateral organization and behavior of lipids in the environment of biological membranes. The idea, that lipids segregate in biological membranes to form liquid-disordered and liquid-ordered states, was faced with a challenge: to show that lipid-ordered domains, enriched in sphingomyelin and cholesterol, actually exist in vivo. A great deal of indirect evidence and the use of lipid-binding probes supported this idea, but there was a lack of tools to demonstrate the existence of such domains in living cells. A whole new toolbox had to be invented to biochemically characterize lipid rafts and to define how they are involved in several cellular functions. A potential solution came from basic biochemical experiments in the late 1970s, showing that some mushroom extracts exert hemolytic activities. These activities were later assigned to aegerolysin-based sphingomyelin/cholesterol-specific cytolytic protein complexes. Recently, six sphingomyelin/cholesterol binding proteins from different mushrooms have been identified and have provided some insight into the nature of sphingomyelin/cholesterol-rich domains in living vertebrate cells. In this review, we dissect the accumulated knowledge and introduce the mushroom lipid raft binding proteins as molecules of choice to study the dynamics and origins of these liquid-ordered domains in mammalian cells.
Highlights
The plasma membrane of cells is a proteolipid bilayer that protects cells from their environment [1,2]
ostreolysin A6 (OlyA6) has revealed a heterogenic pool of membrane domains, and it has been shown to be appropriate for studying the turnover of lipid rafts in living mammalian cells [37]
Panevska et al [64] suggested that pleurotolysin A2 (PlyA2)/PlyB complexes can be used as new bioinsecticides, as discussed for OlyA6/PlyB complexes
Summary
The plasma membrane of cells is a proteolipid bilayer that protects cells from their environment [1,2]. The SM/Chol-binding proteins from the genus Pleurotus (aegerolysins) act as cytolytic proteins when in concert with a partner protein with a membrane attack complex-perforin (MACPF) domain This is not the case for nakanori, which is a lipid raft sensing protein from the mushroom Grifola frondosa (Table 1). We dissect out the accumulated knowledge from recent years, and we introduce the mushroom SM/Chol-binding/sensing proteins ostreolysin A (OlyA) and ostreolysin A6 (OlyA6), recombinant (r)OlyA, pleurotolysin A (PlyA), pleurotolysin A2 (PlyA2), and nakanori as probes for studying lipid rafts in living cells. OlyA6 has revealed a heterogenic pool of membrane domains, and it has been shown to be appropriate for studying the turnover of lipid rafts in living mammalian cells [37]. Serum levels of free fatty acids in mice on a high fat diet treated with rOly were lower than in untreated mice. rOly has, been proposed as an appropriate candidate for treatment of metabolic disorders, such as obesity, hyperlipidemia, and nonalcoholic fatty liver disease
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