Functional Organization of Vertebrate Plasma Membranes:  Molecules to Physiology

Plasma membrane proteins such as ion transporters, cell adhesion molecules, and signaling receptors all must segregate to specific cellular compartments to perform their physiological roles. Our laboratory has discovered an adaptable mechanism based on ankyrins and their spectrin partners that is responsible for coordinating functionally related membrane-spanning proteins within micron-scale domains in diverse vertebrate plasma membranes including excitable membranes in the nervous system and heart. Ankyrins recognize cytoplasmic domains of membrane transporters and cell adhesion proteins (15 protein families identified so far) through independently evolved interactions of intrinsically disordered sequences with a highly conserved peptide-binding groove formed by the ANK repeat solenoid. Ankyrins are coupled to spectrins, which are elongated organelle-sized proteins that form mechanically resilient arrays through crosslinking by specialized actin filaments. In addition, giant vertebrate ankyrins with specialized roles in axons acquired new coding sequences by exon shuffling early in vertebrate evolution. Giant ankyrins are restricted to neurons and are targets for neurodevelopmental mutations.

Honors and Awards

• Investigator. Howard Hughes Medical Institute. 1987 - 2017
• Fellow. American Association for the Advancement of Science. 2013
• Fellow. Association of American Physicians. 2013
• Member. National Academy of Sciences of the USA. 2010
• Fellow. American Academy of Arts and Sciences. 2009
• Merit Award. NIH. 1990
• Member. American Society of Clinical Investigation. 1987
• Outstanding Young Scientist of the year in Maryland, 1982

Education

MD Johns Hopkins University, 1976
PhD Johns Hopkins University, 1975