Foreword

Biomembranes constitute the boundary between the living organism and the external environment, and the function of various proteins on biomembranes is essential for maintaining biological activities. Quantitative comprehension and precise control of protein-mediated transport of various substances across biomembranes are key challenges in biophysics and cell biology, however, dealing with biomembranes, which are multi-component, heterogeneous, and complex systems, is not an easy task. In this Current Topics of Chem. Pharm. Bull. investigators boldly tackling this area of research will present recent advances in biophysical and molecular biological aspects and technology.

In the structural biology of membrane proteins, lipid bilayer particles called nanodisks are being increasingly utilized. In “Applications of Synthetic Polymer Discoidal Lipid Nanoparticles to Biomedical Research,” Masafumi Tanaka at Kobe Pharmaceutical University summarizes the difference in characteristics between nanodisks of apolipoproteins and synthetic polymers and their application to biomedical research. The ability to change the properties of lipid membranes depending on the type of polymer used will be an important feature of nanodisks in structural studies of membrane proteins and their application as delivery vehicles.

Protein–protein interactions in lipid membranes are expected to vary with membrane lipid composition, but detection of these changes is not straightforward. In “Effects of Membrane Cholesterol on Stability of Transmembrane Helix Associations,” Yoshiaki Yano at Mukogawa Women’s University has evaluated the association between transmembrane helices in liposomes by detecting single-pair fluorescence resonance energy transfer using total internal reflection microscopy. This technique has demonstrated that cholesterol stabilizes associations between transmembrane helices in most cases, but destabilizes associations between helices with GXXXG motifs.

The lipid composition of biological membranes differs between the extracellular and cytosolic leaflets. When lipid exchange (flip-flop) occurs between the two leaflets and the lipid composition of the extracellular leaflet is altered, cellular functions are greatly affected. In “Flip-Flop Promotion Mechanisms by Model Transmembrane Peptides,” Hiroyuki Nakao and Minoru Nakano at the University of Toyama introduce proteins that exhibit such functions in living organisms and describe the development of transmembrane peptides with flip-flop promoting ability and their mechanism. Artificial lipid scrambling could be used in the future to control the function of living cells.

Contrary to the aforementioned lipid scrambling which breaks membrane asymmetry, P4-ATPases and ATP-binding cassette (ABC) transporters are enzymes that create asymmetry using metabolic energy, ATP. The former transports amino-phospholipids from the extracellular leaflet to the cytosolic leaflet, while some proteins of the latter transport phosphatidylcholine in the opposite direction and are also involved in the generation of preβ-HDL (i.e., natural nanodisk!). Hye-Won Shin and Hiroyuki Takatsu at Kyoto University present “Regulatory Roles of N- and C-Terminal Cytoplasmic Regions of P4-ATPases,” in which they introduce the regulatory mechanisms of activity and localization of P4-ATPase in mammalian cells, which have been revealed by recent studies.

Of the four ABC transporters belonging to subfamily D, ABCD1–3 localize to peroxisomal membranes and are involved in transporting various acyl-CoAs from the cytosol to the lumen. ABCD4, on the other hand, functions on the lysosomal membrane and transports vitamin B₁₂ from the lumen to the cytosol, a direction opposite from that of other typical ABC transporters. In “Substrate Specificity and the Direction of Transport in the ABC Transporters ABCD1–3 and ABCD4,” Kosuke Kawaguchi at the University of Toyama and Tsuneo Imanaka at Hiroshima International University summarize the membrane targeting mechanisms and physiological functions of these ABCD transporters and discuss the findings on transport mechanisms based on disease-causing mutations and structural studies by cryo-electron microscopy.

Finally, special thanks to the authors who contributed to the preparation of Current Topics in membrane dynamics and membrane transport. I believe that the topics covered in this Current Topics will provide useful insights to many readers of Chem. Pharm. Bull.