Fascin Protrusions in Cell Interactions

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Cell protrusions are outward extensions of the plasma membrane of individual cells that function in sensing the cell environment and in making initial, dynamic adhesions to extracellular matrix and other cells. Cell protrusions can be grouped into two major categories on the basis of morphology: localized, finger-like structures of highly defined shape and various lengths; or broad, irregular extensions of the plasma membrane. A key requirement of all cell protrusions is the need for a rigid cytoskeleton to support the localized extension of the plasma membrane. This is achieved either by a core unipolar bundle of actin microfilaments in finger-like protrusions, or by a combination of radial, rib-like, actin bundles integrated with a dendritic meshwork of microfilaments in the broad, lamellipodial protrusions. From studies of multiple cell types in vertebrates and invertebrates, fascin-1 has emerged as an actin-bundling protein of general importance for a diverse set of cell protrusions with functions in cell adhesion, cell interactions, and cell migration. This review discusses current knowledge of the molecular and cellular properties and functions of fascin, the roles of fascin-based protrusions in the cardiovascular system in health and disease, and areas of future interest.

Section snippets

Roles of Cell Protrusions in Cell Interactions

Cell protrusions are outward extensions of the plasma membrane of individual cells. They are characteristic of animal and ameboid cells, in which the plasma membrane is not limited by a cell wall. By extending outward into the local environment, cell protrusions make initial adhesions to extracellular matrix (ECM) or other cells and sense and interact with the cell environment. Cues received are relayed back to the cell body by cell-signaling mechanisms and influence subsequent cell behavior:

Structure and Binding Properties

Fascin was discovered as a 55-kDa, actin-bundling protein in extracts of sea urchin oocytes and coelomocytes. Subsequent cDNA sequence information revealed this protein to be related to the Drosophila melanogaster singed protein and a human 55-kDa, actin-bundling protein (Bryan et al., 1993, Mosialos et al., 1994). Available complete genome sequences now clarify that a single form of fascin is encoded in the D. melanogaster (Adams et al. 2000), Anopheles gambiae (EAA12061; Holt et al. 2002),

Roles of Fascin Protrusions in the Cardiovascular System in Health and Disease

Many studies of the cellular roles of fascin-1 have relied on myoblasts, neurons, and fibroblasts. However, there are multiple cell types within the cardiovascular system that express fascin-1, as has been documented by immunohistochemistry (Table 1).

Prospective Future Directions

There is considerable cellular and molecular evidence that fascin-based protrusions are important in cell–cell and cell–ECM interactions and contribute to cell migration. The binding of fascin-1 to F-actin is controlled by multiple points of regulation that ensure that actin-bundling activity is made responsive to extracellular cues and occurs appropriately in space and time. We need to understand more of the molecular mechanisms by which diverse extracellular cues—acting through many

Acknowledgements

This research was supported by National Institutes of Health grant GM068073. The author apologizes that not all the primary literature could be cited due to space limitations.

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