Cell Defects, Polarity, Ezrin, and Medical Insights
All non-infectious diseases are caused by cellular defects that translate into dysfunction of organs. Cells generate biochemically and morphologically distinct plasma membrane domains by polarizing their internal structure and biosynthetic pathways. Without this polarity, cells could not perform functions such as transport across epithelia and signal transmission in neurons.
Anthony Bretscher, Molecular Biology and Genetics, is working to understand how cells organize their plasma membrane—morphology and abundance of specific proteins— and how molecular motors pick up, transport, and deliver different specific cargos. Knowledge about these processes is important, as defects in these processes contribute to many diseases, including cancer.
Bretscher is researching how structural elements and signaling pathways converge to define the morphology of a specific membrane domain. His lab has already defined the major structural components and provided insight into regulation of the critical microfilament-membrane linking protein ezrin (named in honor of Ezra Cornell). The lab is now elucidating the signaling pathways that impinge on ezrin to determine how microvilli impact the membrane proteome, and identifying the additional functions and regulators of ezrin.
Bretscher is also studying how motor-based transport along microfilaments is coordinated with membrane traffic, using yeast as a model organism. As the molecules involved are conserved between yeast and vertebrates, the findings will be of general significance. The research is providing fundamental and medically relevant insights into critical aspects of cell polarity.
NIH Award Number: 1R35GM131751-01