The Journal of Membrane Biology

Gerle, Christoph

doi: 10.1007/s00232-019-00061-wpmid: 30877332

Of all the macromolecular assemblies of life, the least understood is the biomembrane. This is especially true in regard to its atomic structure. Ideas on biomembranes, developed in the last 200 years, culminated in the fluid mosaic model of the membrane. In this essay, I provide a historical outline of how we arrived at our current understanding of biomembranes and the models we use to describe them. A selection of direct experimental findings on the nano-scale structure of biomembranes is taken up to discuss their physical nature, and special emphasis is put on the surprising insights that arise from atomic scale descriptions.

Balleza, Daniel; Alessandrini, Andrea; Beltrán García, Miguel

doi: 10.1007/s00232-019-00067-4pmid: 31098678

Several experimental and theoretical studies have extensively investigated the effects of a large diversity of antimicrobial peptides (AMPs) on model lipid bilayers and living cells. Many of these peptides disturb cells by forming pores in the plasma membrane that eventually lead to the cell death. The complexity of these peptide–lipid interactions is mainly related to electrostatic, hydrophobic and topological issues of these counterparts. Diverse studies have shed some light on how AMPs act on lipid bilayers composed by different phospholipids, and how mechanical properties of membranes could affect the antimicrobial effects of such compounds. On the other hand, cyclic lipopeptides (cLPs), an important class of microbial secondary metabolites, have received comparatively less attention. Due to their amphipathic structures, cLPs exhibit interesting biological activities including interactions with biofilms, anti-bacterial, anti-fungal, antiviral, and anti-tumoral properties, which deserve more investigation. Understanding how physicochemical properties of lipid bilayers contribute and determining the antagonistic activity of these secondary metabolites over a broad spectrum of microbial pathogens could establish a framework to design and select effective strategies of biological control. This implies unravelling—at the biophysical level—the complex interactions established between cLPs and lipid bilayers. This review presents, in a systematic manner, the diversity of lipidated antibiotics produced by different microorganisms, with a critical analysis of the perturbing actions that have been reported in the literature for this specific set of membrane-active lipopeptides during their interactions with model membranes and in vivo. With an overview on the mechanical properties of lipid bilayers that can be experimentally determined, we also discuss which parameters are relevant in the understanding of those perturbation effects. Finally, we expose in brief, how this knowledge can help to design novel strategies to use these biosurfactants in the agronomic and pharmaceutical industries.

Tabbasum, Valentina; Cooper, Dermot

doi: 10.1007/s00232-019-00060-xpmid: 30746562

The fidelity of cAMP in controlling numerous cellular functions rests crucially on the precise organization of cAMP microdomains that are sustained by the scaffolding properties of adenylyl cyclase. Earlier studies suggested that AC8 enriches in lipid rafts where it interacts with cytoskeletal elements. However, these are not stable structures and little is known about the dynamics of AC8 secretion and its interactions. The present study addresses the role of the cytoskeleton in maintaining the AC8 microenvironment, particularly in the context of the trafficking route of AC8 and its interaction with caveolin1. Here, biochemical and live-cell imaging approaches expose a complex, dynamic interaction between AC8 and caveolin1 that affects AC8 processing, targeting and responsiveness in plasma membrane lipid rafts. Site-directed mutagenesis and pharmacological approaches reveal that AC8 is processed with complex N-glycans and associates with lipid rafts en route to the plasma membrane. A dynamic picture emerges of the trafficking and interactions of AC8 while travelling to the plasma membrane, which are key to the organization of the AC8 microdomain.

Khoury, Mario; Winterstein, Tobias; Weber, Wadim; Stein, Viktor; Schlaak, Helmut; Thiel, Gerhard

doi: 10.1007/s00232-019-00062-9pmid: 30863900

Huang, Li-Kun; Liao, Ya-Yun; Lin, Wei-Hua; Lin, Shih-Ming; Liu, Tzu-Yin; Lee, Ching-Hung; Pan, Rong-Long

doi: 10.1007/s00232-019-00065-6pmid: 31053903

Auxin regulates diverse processes involved in plant growth and development. AUX1 is the first identified and most widely investigated auxin importer, and plays an important role in root gravitropism and the development of lateral root and root hair. However, the regulation of auxin transport by AUX1 is still not well understood. In this study, we examined the effect of metal ions on AUX1 transport function and found that the activity could be specifically stimulated four times by K+. Further experiments revealed the preference of KF on the enhancement of transport activity of AUX1 over KCl, KBr, and KI. In addition, the interaction between K+ and AUX1 confers AUX1 more resistant to thermal stress but more vulnerable to proteolysis. Conventional chemical modification indicated that the extracellular acidic amino acids of AUX1 play a key role in the K+ stimulation. Site-specific mutagenesis showed that the replacement of Asp166, Asp293, and Asp312 of AUX1 to alanine deteriorated the K+-stimulated auxin transport. By contrast, when these residues were mutated to glutamate, lysine, or asparagine, only the D312E variant restored the IAA transport activity to the wild-type level. It is thus convinced that D312 is presumably the most promising residue for the K+ stimulation on AUX1.

George, Kiran; Thomas, Nisha; Malathi, Raman

doi: 10.1007/s00232-019-00070-9pmid: 31165179

Phytochemicals are ubiquitous in naturally occurring dietary elements that exhibits diverse pharmacological properties over various pathological disorders, including cancer. Voltage gated K+ (KV) channel in the plasma membrane contributes to wide range of cellular processes including cancer progression. Therefore, modulation of KV channel is being considered as a novel potential target for cancer therapy. The whole cell patch clamp technique was used to record the modulatory effect of chrysin, naringenin, caffeic acid, gallic acid, and zingerone on delayed rectifier potassium current (I K) in human prostate cancer cells LNCaP and PC-3. Among the tested compounds, zingerone blocked I K in a concentration-dependent manner in LNCaP cells and estimated the IC50 value of 141 μM and E max was 81.3%. Further analysis of KV channel activation kinetics showed that zingerone induces a positive shift in the activation curve in LNCaP cells, whereas the inhibitory effect of gallic acid on I K was significantly less potent than the inhibition caused by zingerone. However, chrysin, naringenin, and caffeic acid did not modulate the KV channel conductance in LNCaP or PC-3 cells. Our findings confirmed that not all the tested phytochemicals to be effective modulators of I K and suggested that I K inhibitory effect of zingerone and gallic acid may be responsible for their anticancer effects in prostate cancer cells.