April 2011

Special Symposium: Na,K-ATPase and related P-type ATPases: structure, biology and medicine

The four-day meeting will have sessions devoted to structure and mechanism, cell biology and trafficking, regulation, signaling, and mechanisms in physiology and medicine.

Kathleen Sweadner


The Na,K-ATPases, Ca2+-ATPases and their relatives have extremely important physiological roles as transporters. They are much more than ion pumps, however, as they also play complex roles in cell biology that were unimagined 10 to 15 years ago. The interdisciplinary “Na,K-ATPase and related P-type ATPases: structure, biology and medicine” meeting will bring together biochemists, physiologists, doctors, geneticists and cell biologists with shared interests in this subject.

The P-type ATPases are membrane proteins that catalyze uphill transport via the hydrolysis of ATP. They are found in all domains of life. The group is named for the labile covalent phosphorylation of an aspartate residue as part of the reaction mechanism, and its members share essential structural features. Eleven human diseases caused by mutations in different P-ATPases have been found, and many more are thought to exist. Multiple crystal structures of the muscle Ca2+-ATPase SERCA in different conformations have resulted in dynamic models of its mechanism.

Physiological regulation of transport occurs at multiple levels, which is consistent with the many indispensible biological roles of P-type ATPases. The enzymes are major pharmacological targets, notably for digitalin and omeprazole in humans, and they also are essential for many pathogens. While the subject of this meeting is focused narrowly enough to keep it cohesive, the scope of new discoveries and medical implications in the field is expanding rapidly.

The textbook concept of ATPases as ion pumps was turned upside down by the discovery that the Na,K-ATPase also is a signaling molecule integrated into the control of cell proliferation and hypertrophy with transport-independent roles in a number of diseases. It signals through interaction with either Src or the IP3 receptor. More recently, a completely new and unrelated role has emerged for subunits of Na,K-ATPase in intercellular adhesion and cell junction structure and function and thus in tissue morphogenesis and cancer. Many of the really novel recent discoveries in P-type ATPases have encompassed such noncanonical roles.

Because P-ATPases are so diverse and widespread, no single national meeting attracts a critical mass of interdisciplinary experts in this field, who can range from crystallographers to clinicians. Few other meetings give the opportunity for cancer biologists interested in growth control or the modulation of cell adhesion to see where their interests intersect with those of cardiologists investigating contractility or endogenous ligands or neurobiologists investigating the basis of genetic defects, and then to relate these findings to atomic-level structures. This American Society for Biochemistry and Molecular Biology event continues a tradition of holding international meetings on P-ATPases that are attended by experts from all over the world every three years.

The meeting will be four days long with sessions devoted to structure and mechanism, cell biology and trafficking, regulation, signaling, and mechanisms in physiology and medicine. Invited speakers will discuss several kinds of calcium ATPases, Na,K-ATPases and H,K-ATPases, copper ATPases, proton ATPases and the exciting area of lipid flippases. The meeting scope will include the structures and the remarkable conformational dynamics of this class of molecules; mutations in mechanistic studies and in human disease; regulatory networks, trafficking and complexes associated with ATPases; the drugs and endogenous ligands that bind to ATPases; and the enzymes’ unique regulatory proteins, such as phospholamban and FXYDs.

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