A new finding: Nudel and FAK as Antagonizing Strength Modulator of Nscent Adhesions through Paxillin

Research team led by Prof. Xueliang Zhu at SIBCB has recently found a novel mechanism for selective reinforcement of nascent adhesion via interplays of Nudel and FAK with Paxillin to facilitate cell migration. The work was published on PLoS Biology on May 26th.

 

Cell migration is an essential process in both single-cell and multicellular organisms. In higher animals, cell migration is important for many biological processes, including embryonic development, the immune response, and wound healing. Cancer cell invasion into healthy tissues occurs as a result of inappropriate cell migration. As can be easily visualized when cultured in the lab, mammalian cells attach to surfaces through focal adhesions, cellular structures characterized by complexes of the transmembrane protein integrin and intracellular proteins including paxillin and focal adhesion kinase (FAK). In order for cells to move, they must coordinate two processes: extension of the front edge of the cell and retraction of the back edge. To accomplish this, a cell first protrudes membranous structures from the front edge and then establishes tiny adhesion structures known as nascent adhesions to hold the extensions in place. At the same time, the focal adhesions that hold a cell in place must be disrupted in order for the back edge of the cell to retract. Focal adhesions are huge in size as compared to nascent adhesions. Nevertheless, for unknown reasons they appear less resistant to retraction forces than nascent adhesions do.

 

The scientists found that a protein called Nudel interacted with paxillin and was enriched at the front edge of moving cells. Depletion of Nudel by interference RNA resulted in shrinkage of cell edges due to inefficient formation of nascent adhesion (A). They further showed that FAK was able to disrupt the Nudel-paxillin interaction in a kinase-independent manner. Moreover, overexpressing the paxillin-binding domain of FAK or full-length FAK mutant that was devoid of its self-inhibitory conformation also led to cell edge shrinkage. Therefore, they proposed the following model (B): the Nudel-paxillin interaction enhances the strength of nascent adhesions to promote the attachment of membrane protrusions at the front edge of the cell, whereas FAK prevents the Nudel-paxillin interaction in focal adhesions in order to facilitate retraction of the back edge of the cell.