Caveolin-1 Endows Order in Cholesterol-Rich Detergent Resistant Membranes

Raggi, Carla; Diociaiuti, Marco; Caracciolo, Giulio; Fratini, Federica; Fantozzi, Luca; Piccaro, Giovanni; Fecchi, Katia; Pizzi, Elisabetta; Marano, Giuseppe; Ciaffoni, Fiorella; Bravo, Elena; Fiani, Maria L.; Sargiacomo, Massimo

doi:10.3390/biom9070287

Cited by 13 publications

(10 citation statements)

References 50 publications

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“…While some proteins are thought to passively associate with raft-like domains, others can actively promote their formation by clustering raft components and stabilizing ordered domains (25,59). Proteins that modulate membrane order or fluidity also are capable of regulating phase separation (60,61). Here, we identify PMP22 as a new example of a protein that can directly stabilize ordered phase membrane domains.…”

Section: Pmp22 Stabilizes Ordered Phase Domains and Promotes Their Fomentioning

confidence: 95%

Peripheral Myelin Protein 22 Preferentially Partitions into Ordered Phase Membrane Domains

Marinko

Kenworthy

et al. 2020

Preprint

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The ordered environment of membrane rafts is thought to exclude many transmembrane proteins. Nevertheless, some multi-pass transmembrane proteins have been proposed to partition into ordered domains. Here, giant plasma membrane vesicles (GPMVs) were employed to quantitatively show that the tetraspan peripheral myelin protein 22 (PMP22) exhibits a pronounced preference for, promotes the formation of, and stabilizes ordered membrane domains. Neither S-palmitoylation of PMP22 nor its putative cholesterol binding motifs are required for partitioning to ordered domains. In contrast, disruption of its unusual first transmembrane helix (TM1) reduced ordered phase preference. Charcot-Marie-Tooth disease-causing mutations that destabilize PMP22 also reduced or eliminated this preference in favor of the disordered phase. These studies demonstrate PMP22’s ordered phase preference derives both from the distinctive properties of TM1 and global structural features associated with its transmembrane domain, providing a first glimpse at the structural factors that promote raft partitioning for multi-pass proteins.Significance StatementThe preferential partitioning of single span membrane proteins for the ordered phase of ordered/disordered phase-separated membranes is now reasonably well understood, but little is known about this phase preferences of multi-pass membrane proteins. Here, it is shown that the disease-linked tetraspan integral membrane protein, PMP22, displays a pronounced preference to partition into the ordered phase, a preference that is reversed by disease mutations. This phase preference may be related to the role of PMP22 in cholesterol homeostasis in myelinating Schwann cells, a role that is also known to be disrupted under conditions of CMTD peripheral neuropathy caused by pmp22 mutations.

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Section: Pmp22 Stabilizes Ordered Phase Domains and Promotes Their Fomentioning

confidence: 95%

Peripheral Myelin Protein 22 Preferentially Partitions into Ordered Phase Membrane Domains

Marinko

Kenworthy

et al. 2020

Preprint

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“…Because of their dynamic nature the proportions of raft to non-raft membrane lipids are difficult to quantify and image in real time. The most common method to study lipid raft composition is to isolate detergentresistant membrane (DRM) from cells (15). DRM from model membranes and cell membranes contain a subset of lipid-anchored and integral plasma-membrane proteins.…”

Section: Microdomains and Cellular Cholesterol Homeostasismentioning

confidence: 99%

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

Ouweneel

Thomas

Sorci‐Thomas

2020

Journal of Lipid Research

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Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.

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“…Bilayer domains also can be organized and ordered by proteins; for example, by caveolins (Section 4.8). 35 …”

Section: Cholesterol Complexes With Phospholipidsmentioning

confidence: 99%

Active cholesterol 20 years on

Lange

Steck

2020

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This review considers the following hypotheses, some well‐supported and some speculative. Almost all of the sterol molecules in plasma membranes are associated with bilayer phospholipids in complexes of varied strength and stoichiometry. These complexes underlie many of the material properties of the bilayer. The small fraction of cholesterol molecules exceeding the binding capacity of the phospholipids is thermodynamically active and serves diverse functions. It circulates briskly among the cell membranes, particularly through contact sites linking the organelles. Active cholesterol provides the upstream feedback signal to multiple mechanisms governing plasma membrane homeostasis, pegging the sterol level to a threshold set by its phospholipids. Active cholesterol could also be the cargo for various inter‐organelle transporters and the form excreted from cells by reverse transport. Furthermore, it is integral to the function of caveolae; a mediator of Hedgehog regulation; and a ligand for the binding of cytolytic toxins to membranes. Active cholesterol modulates a variety of plasma membrane proteins—receptors, channels and transporters—at least in vitro.

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Caveolin-1 Endows Order in Cholesterol-Rich Detergent Resistant Membranes

Cited by 13 publications

References 50 publications

Peripheral Myelin Protein 22 Preferentially Partitions into Ordered Phase Membrane Domains

Peripheral Myelin Protein 22 Preferentially Partitions into Ordered Phase Membrane Domains

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

Active cholesterol 20 years on

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