How Do Our Cells Know Where They’re Going?

By Jeffrey Norris

This screen shot of a migrating human skin cell shows focal adhesion sites with which cells attach to the extracellular matrix in purple, and receptors that link microtubules to focal adhesions in two different proteins in the same pathway. A movie showing the cell's movement, which can be seen here, was captured by spinning disk confocal microscopy of fluorescently labeled proteins and is displayed with inverted contrast. Courtesy of Torsten Wittmann, PhD

You might think you look relatively the same from day to day, but inside, your cells are moving about, helping you to keep it all together. How they do it holds fascination for cell biologists and is of vital importance for ensuring normal development, or for learning how cancers spread. Many mysteries of cell movement remain.

“Cells aren’t just bags of proteins, but have a marvelously complex and dynamic internal organization,” said UCSF cell biologist Torsten Wittmann, PhD, an associate professor of cell and tissue biology with the UCSF School of Dentistry, who probes cell dynamics deeply to figure out how they move the way they do.

Clearly, they don’t move randomly. In tissues, cells travel through microscopic scaffolding, called the extracellular matrix (ECM), changing their shapes and following tracts in a seemingly purposeful way.

Torsten Wittmann, PhD

Wittmann has just made a key discovery of a molecular process that is a lynchpin in permitting the directional movement of cells.  He found that a protein called CLASP enables the timely dissolution of structures called focal adhesions. CLASPs keep cells inching along the matrix by permitting the localized secretion of ECM-dissolving enzymes underneath the cell, allowing the cell to move forward in a coordinated manner. Wittmann’s study, with many striking live-cell images, is reported online May 25 in the journal Nature Cell Biology.

“There are hot spots of secretion that correspond to where cells attach to the extracellular matrix,” Wittmann said.

It’s as if there is a seamless link between the cell’s internal mechanisms and the constantly remodeling ECM outside the cell. Long filaments called microtubules, which carry molecular cargoes to the cell surface for local release, are linked to focal adhesions through CLASP proteins.

Wittmann is exploring use of light-activated molecules to change cellular dynamics. “If we could locally manipulate microtubule behavior within particular regions of cells, we would learn more about how cell dynamics are controlled, and would expect that we could alter cell movement,” he said.

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