Vann Bennett

George Barth Geller Distinguished Professor of Molecular Biology
Vann Bennett
Vann Bennett

Overview

A major interest of our laboratory is in understanding how cells in metazoan organisms manage to target ion channels to physiological sites that optimize their physiological efficiency. Our research began with discovery of the ankyrin family of membrane-adapter proteins, which interact with structurally diverse membrane proteins and couple these proteins to the spectrin-based membrane skeleton. Currently identified ankyrin partners are anion exchangers, the Na/K ATPase, the voltage-dependent sodium channel, and the Na/Ca exchanger. Ankyrin(s) also associate with calcium-release channels including both IP3 and ryanodine receptors. Finally, ankyrins also bind to cell adhesion molecules of the L1 CAM family (L1/neurofascin/NrCAM/NgCAM in vertebrates; neuroglian in Drosophila; LAD-1 in C. elegans). Ankyrins interact with these diverse proteins through a motif known as ANK repeats, which are found in many different proteins and operate in protein recognition for multiple structurally unrelated ligands.
We have recently reported that humans heterozygous for a E1425G loss-of-function mutation in ankyrin-B and mice heterozygous for a null mutation in ankyrin-B have type 4 long QT syndrome, a cardiac arrhythmia associated with sudden cardiac death. We also have discovered that ankyri9n-B mutation results in reduced levels of Na/Ca exchanger, Na/K ATPase, and IP3 R at T-tubule sites in cardiomyocytes and leads to altered Ca2+ signaling and extrasystoles that provide a rationale for the arrhythmia. This work has identified a new mechanism for cardiac arrhythmia due to abnormal co-ordination of multiple functionally related ion channels and transporters. We have also found that conditional knockout of ankyrin-G in the mouse cerebellum results in severe ataxia accompanied by coordinate loss of the sodium channel Nav1.6, neurofascin (a member of the L1CAM family), and beta IV spectrin from axon initial segments. These studies, together with the role of ankyrin-B in type 4 long QT syndrome, establish a physiological requirement for ankyrins in localization of a variety of ion channels in excitable membranes in the heart and nervous system, and suggest a new class of functional channelopathies due to abnormal cellular localization.
Future research will be based on the discovery that ankyrin-B and ankyrin-G have physiological roles as coordinators of multiple functionally related proteins in specialized cell membrane compartments. A major effort will be to understand mechanisms, beginning at a protein level with ankyrin-B structure and function, and including the cellular basis for ankyrin-B-dependent protein sorting in cardiomyocytes. We also plan to study the roles of ankyrins B and G in ion channel organization in the visual system using targeted gene knockouts in rods, retinal ganglion neurons, and retinal pigmented epithelial cells (mice with loss of function may be blind but should be viable).

Positions

George Barth Geller Distinguished Professor of Molecular Biology in the School of Medicine

2012 School of Medicine

Professor Emeritus of Biochemistry in the School of Medicine

2023 School of Medicine

Member of the Duke Cancer Institute in the School of Medicine

1987 School of Medicine

Education

Ph.D. 1975

1975 Johns Hopkins University

M.D. 1976

1976 Johns Hopkins University

Publications, Grants & Awards

Offices & Contact

214A Nanaline H Duke
Durham, NC
27710
Box 3711 Med Ctr
Durham, NC
27710