ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans.

Bafilomycins and concanamycins, two groups of the plecomacrolide-defined class of macrolide antibiotics, have recently been recognized as important tools for studying the physiological role of vacuolar-type, proton-translocating ATPases (V-ATPases) and ATPases with phosphorylated states (P-ATPases) in animal and plant cells as well as in yeast, fungi and bacteria. The following review will give an account of the classification and function of these antibiotics.

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Bafilomycins and concanamycins as inhibitors of V-ATPases and P-ATPases.

Interleukin 1beta (IL-1beta), a secretory protein lacking a signal peptide, does not follow the classical endoplasmic reticulum-to-Golgi pathway of secretion. Here we provide the evidence for a "leaderless" secretory route that uses regulated exocytosis of preterminal endocytic vesicles to transport cytosolic IL-1beta out of the cell. Indeed, although most of the IL-1beta precursor (proIL-1beta) localizes in the cytosol of activated human monocytes, a fraction is contained within vesicles that cofractionate with late endosomes and early lysosomes on Percoll density gradients and display ultrastructural features and markers typical of these organelles. The observation of organelles positive for both IL-1beta and the endolysosomal hydrolase cathepsin D or for both IL-1beta and the lysosomal marker Lamp-1 further suggests that they belong to the preterminal endocytic compartment. In addition, similarly to lysosomal hydrolases, secretion of IL-1beta is induced by acidotropic drugs. Treatment of monocytes with the sulfonylurea glibenclamide inhibits both IL-1beta secretion and vesicular accumulation, suggesting that this drug prevents the translocation of proIL-1beta from the cytosol into the vesicles. A high concentration of extracellular ATP and hypotonic medium increase secretion of IL-1beta but deplete the vesicular proIL-1beta content, indicating that exocytosis of proIL-1beta-containing vesicles is regulated by ATP and osmotic conditions.

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The Secretory Route of the Leaderless Protein Interleukin 1β Involves Exocytosis of Endolysosome-related Vesicles

Members of the superfamily of adenosine triphosphate (ATP)-binding-cassette (ABC) transport systems couple the hydrolysis of ATP to the translocation of solutes across a biological membrane. Recognized by their common modular organization and two sequence motifs that constitute a nucleotide binding fold, ABC transporters are widespread among all living organisms. They accomplish not only the uptake of nutrients in bacteria but are involved in diverse processes, such as signal transduction, protein secretion, drug and antibiotic resistance, antigen presentation, bacterial pathogenesis and sporulation. Moreover, some human inheritable diseases, like cystic fibrosis, adrenoleukodystrophy and Stargardt's disease are caused by defective ABC transport systems. Thus, albeit of major significance, details of the molecular mechanism by which these systems exert their functions are still poorly understood. In this review, recent data concerning the properties and putative role of the ATP-hydrolyzing subunits/domains are summarized and compared between bacterial and eukaryotic systems.

ATP‐binding‐cassette (ABC) transport systems: Functional and structural aspects of the ATP‐hydrolyzing subunits/domains

Crystal Structures of the MJ1267 ATP Binding Cassette Reveal an Induced-Fit Effect at the ATPase Active Site of an ABC Transporter

Vanadate and Bafilomycin A1 Are Potent Inhibitors of the ATPase Activity of the Reconstituted Bacterial ATP-Binding Cassette Transporter for Maltose (MalFGK2)

E. Schneider

Papers

Vanadate and Bafilomycin A1 Are Potent Inhibitors of the ATPase Activity of the Reconstituted Bacterial ATP-Binding Cassette Transporter for Maltose (MalFGK2)