Focal adhesions and stress fiber formation. (a) Syndecan-4 is diffusely distributed in the membrane, as is the phospholipid PIP2 (yellow). PKCα (red ovals) is cytosolic under these conditions. (b) Following interaction with ligand (blue), syndecan-4 becomes clustered into forming focal adhesions. This clustering is stabilized by PIP2 and allows binding and superactivation of PKCα, leading to the phosphorylation of focal adhesion proteins. The actin microfilament system is condensed at focal adhesions, inducing the formation of stress fibers. Shed forms of syndecan-4 may interfere with the cell’s ability to reorganize its cytoskeleton in response to adhesive interactions. The function of syndecan-4, either in its membrane-bound form or in solution, is analogous to that of a number of matricellular proteins described elsewhere in this Perspective series.