Effects of Membrane Lipids on Protein Function

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Background

Eukaryotic homeostasis requires the trafficking of cargo between membrane bound organelles. Generally, cargo vesicles are budded from a donor compartment, transported, and fused to an acceptor organelle to deliver cargo. While the membrane associated proteins that drive each of these steps including coat protein complexes, Rab GTPases and their effectors, and SNAREs are well known, their regulation by the membrane itself remains enigmatic. The lipid bilayer imposes two major influences on membrane proteins. These effects can be distinguished as specific protein-lipid interactions at a chemical level, and non-specific interactions that occur at a physical level. Protein function can be affected by many physical parameters including, bilayer thickness, fluidity, and curvature. Membrane thickness itself can be modulated by sterol content as well as acyl chain length, and can have profound effects on protein function. Taken together, the effects of the membrane on protein function and cargo trafficking is striking.

Investigating how lipids affect protein function can be separated into two major areas:

Lipid modification – The lipid composition of membranes is not static and the local stoichiometry of a membrane can be rapidly altered to drive the transitions through a pathway. Lipids such as phosphoinositides can be differentially phosphorylated and dephosphorylated by specific kinases and phosphatases. Such changes not only affect the recruitment of proteins with specific lipid binding domains, but alter the local surface charge of a membrane. Lipids can also be modified through the action of various phospholipases to remove lipid head groups or acyl chains to make lysolipids and affect membrane curvature. The removal of acyl changes can also be coupled with their exchange through the action of acyltransferases. Other modifications that can alter lipid function, and in turn, protein function occurs through the glycosylation of head groups and desaturation of acyl chains.

Lipid organization – The landscape of a membrane surface can be drastically altered to affect protein function and cellular pathways. Changing the characteristic of a leaflet can occur through translocating lipids across the bilayer through the function of flippases, floppases and scramblases to establish or destroy lipid asymmetry. Other modifications occur through non-vesicular lipid transfer between membranes. Finally, the physical characteristics of a membrane can change through the formation of sterol and sphingolipid rich membrane microdomains formation that both thicken and stiffen membranes to affect protein function. These modifications along with lipid interdigitation, hydrophobic mismatching, and membrane compression can exquisitely regulate protein function and their pathways.

The aim of this Research Topic is to cover recent and novel work that will further elucidate the effects of membrane lipids on protein function. Areas to be covered in this Research Topic may include, but are not limited to:

1. Phosphoinositides in the endolysosomal pathway
2. Lipid rafts/Cholesterol & trafficking
3. Lipid exchange proteins
4. Lipid droplet trafficking
5. Cardiolipin & Mitochondria
6. Lipids and autophagy
7. Tuberculosis and PIPs
8. PIP acyl function
9. Phosphoinositides and pathogens
10. Legionella and lipid modifying effectors
11. Cholesterol and pathogens
12. Xenophagy and Lipids
13. Lipid signaling & Viruses
14. Lipids in nucleus
15. Molecular dynamics of membrane curvature
16. Membrane fluidity and mechanosensitive channels
17. Sphingolipids and actin remodeling
18. Membrane tension and vesicle fission/fusion
19. Acyl chain length and hydrophobic mismatch
20. Membrane compression
21. Lipid composition and ion transport
22. Lipid flippases, floppases and scrablases
23. Acyl chain asymmetry/polyunsaturation
24. Glycosphingolipids and Lyn signaling
25. Omega lipids and SNARE activation
26. Lipid composition in exosomes
27. Lipid composition in microvesicles
28. Lipidation and traffic of morphogens
29. lipid and membrane traffic in cilia in vivo
30. Membrane traffic and membrane composition in cell adhesion and tissue morphogenesis
31. Interorganelle contacts, lipid droplets in cellular and organismal stress
32. Lipids and Rab function
33. Sphingolipids in synapse structure and function

Keywords: Phosphoinositides, Lipid Rafts, Lipid Droplet, Sphingolipid, Cardiolipin

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