Mark Berryman, Ph.D.

     The cortex of animal cells consists of the plasma membrane and an underlying meshwork of actin filaments.  The structure and function of the cortex varies tremendously among cells, and this variation is reflected by the diversity of highly specialized cell types within the body.  I am interested in understanding the molecular basis for the regulation of cortical structure and function, particularly in polarized epithelia. Polarized epithelia line all body cavities  and are rich in organs involved in secretion and absorption.  A hallmark of polarized epithelial cells is the organization of the plasma membrane into distinct apical and basolateral domains, a feature that is crucial to vectorial transport processes.  M y research focuses mainly on the apical domain, which is characterized by the presence of microvilli, finger-like projections that increase the surface area and enhance transport capacity.  The microvilli are supported by a bundle of actin filaments which attach to proteins embedded in the plasma membrane through linker molecules.  Examples of linker molecules include ezrin, radixin, and moesin, a family of related proteins that play a role in the assembly and maintenance of microvilli.  Ezrin, which can exist in monomeric or oligomeric form, is believed to undergo conformational changes that expose hidden binding sites both for actin filaments and membrane proteins.  Regulated changes in the conformation of ezrin are likely to accompany the formation of microvilli in many polarized cells.  How is the conformation of ezrin regulated?  How are other protein-protein interactions regulated during the assembly of microvilli?  These types of questions are being addressed using microvilli isolated from human placenta as a model system to study interacting components in vitro.  Using this system, I have identified a novel protein that associates with the actin cytoskeleton and appears to be involved in chloride transport.  This discovery is particularly exciting because defective ion transporters have been implicated in several diseases including cystic fibrosis and cholera.

Selected References:

• Berryman, M., and A. Bretscher (2000) Identification of a novel member of the chloride intracellular channel gene family (CLIC5) that associates with the actin cytoskeleton of placental microvilli. Mol. Biol. Cell 11:1509-1521.

• Bretscher, A., and M. Berryman (1999) In Guidebook to the Cytoskeletal and Motor Proteins (T. Kreis and R. Vale, eds.), Oxford University Press, New York.

• Bretscher, A., D. Reczek, and M. Berryman (1997) Ezrin: a protein requiring conformational activation to link microfilaments to the plasma membrane in the assembly of cell surface structures.  J. Cell Sci. 110:3011-3018.

• Reczek, D., M. Berryman, and A. Bretscher (1997) Identification of EBP50: a PDZ-containing phosphoprotein that associates with members of the ERM family.  J. Cell Biol. 139:169-179.

• Berryman, M., R. Gary, and A. Bretscher (1995) Ezrin oligomers are major cytoskeletal components of placental microvilli: a proposal for their involvement in cortical morphogenesis.  J. Cell Biol. 131:1231-1242.

• Bretscher, A., R. Gary, and M. Berryman (1995) Soluble ezrin purified from human placenta exists as stable monomers and elongated dimers with masked c-terminal ezrin-radixin-moesin association domains.  Biochemistry 34:16830-16837.