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RESEARCH INTERESTS
Membrane-cytoskeletal interactions; cell adhesion; cytoskeleton
Understanding the molecular mechanism of cell movement
Signaling from the cell surface to the nucleus
How is the contractile machinery of muscle cells established and maintained?
PUBLICATIONS
Adhesion to extracellular ligands can induce profound
changes in cell behavior ranging from alteration in cell
morphology to induction of specific gene expression. We are
studying how cell adhesion is regulated and how interaction
with extracellular matrix can trigger changes in the
differentiation state or developmental fate of a cell.
In order to understand how transmembrane signaling occurs
at sites of cell adhesion, it is necessary first to understand
the molecular architecture at sites of membrane-substratum
contact. A useful model system for studying adhesive
membranes is the focal contact or adhesion plaque of
cultured cells. One of our goals is to identify the protein
constituents of the adhesion plaque and define their
individual functions.
We recently identified an interesting component of adhesion
plaques, called zyxin, which may play a role in signal
transduction in response to cell adhesion to extracellular
matrix. Zyxin is a low abundance protein that has a proline-
rich N-terminus and three LIM domains at its C-terminus. LIM
domains are zinc-binding structural motifs that have been
identified in a number of proteins that are involved in
differentiation and the control of gene expression. For
example, LIM domains have been identified in DNA-binding
homedomain proteins from Drosophila, C. elegans, mouse,
and Xenopus. From our work we suspect that LIM domains
function as protein-binding interfaces that regulate the
subcellular localization or biological activity of the LIM-domain
proteins. The fact that zyxin displays LIM repeats raises the
intriguing possibility that zyxin is one of the long sought
proteins involved in coupling the mechanical events of cell
adhesion to the cellular machinery required to affect the
differentiation state or developmental fate of cell. Our future
work will utilize molecular and biochemical approaches to
identify proteins that might interact with zyxin and to define
the specific role of zyxin at adhesion plaques.
Adhesion plaques are dynamic structures that can be
assembled and disassembled. One very interesting question
that remains to be addressed is how cells regulate their
association with extracellular ligands. To examine this
problem, we are studying platelets, the cells in the body
responsible for blood clotting. Platelets exhibit highly
regulated adhesion. Resting platelets in vivo are non-
adhesive cells; however, when they encounter a discontinuity
in a blood vessel wall they become activated and develop
adhesive potential. We are studying the early stages in the
development of platelet adhesion in an attempt to define the
temporal sequence of events that gives rise to a mature
adhesive membrane in an activated platelet. We have found
that platelets are a rich source of adhesion plaque proteins
and these proteins are likely to be involved in the generation
and control of platelet adhesion. By the study of these
specialized cells, we hope to learn how cell adhesion is
regulated.
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