The molecular organization of plasma membranes in differentiated vertebrate cells and to the role of such cellular-level structure in normal physiology and disease.
Membrane-spanning proteins such as ion transporters, cell adhesion molecules, and signaling receptors all must segregate to specific cellular locations to perform their physiological roles in our bodies. Deciphering the molecular basis for plasma membrane polarity is an interdisciplinary problem at the interface of cell biology, physiology, and clinical medicine. Our laboratory has discovered the ankyrin family of adapters and their role in the organization of a surprisingly diverse set of proteins and membrane domains that are likely to play pervasive roles in vertebrate physiology. We have resolved a simple "code" for ankyrin binding by membrane proteins that has independently evolved in many protein families, including those such as voltage-gated sodium channels with specialized roles in vertebrates. We have found that ankyrin proteins are required for coordination of functionally related membrane partners within specialized membrane domains, including axon initial segments of neurons, lateral membrane domains of epithelial cells, inner and outer segments of photoreceptors, and costameres of striated muscle. We are exploring the molecular mechanisms underlying ankyrin function as well as the pathological consequences—such as cardiac arrhythmia and diabetes—when these mechanisms fail.