Liberating TGFβ

Overactive TGFβ spurs Marfan's syndrome, which might have been responsible for Abraham Lincoln's rangy physique. But how the molecule gets released from storage and switched on is uncertain. On page 355 Chaudhry et al. fill in a key step, showing that a piece of an extracellular matrix (ECM) protein frees inert TGFβ.

TGFβ helps control whether cells move, divide, specialize, and survive. Cells often lock up the potent cytokine by fastening a complex containing its inactive form to fibrillin-1 fibers in the ECM. Discovering how this sequestered TGFβ breaks loose might clarify the mechanism of Marfan's syndrome, in which fibrillin-1 mutations lead to symptoms such as a weakened aorta and leaky heart valves.

Chaudhry et al. demonstrated that fibrillin-1 itself helps release the TGFβ complex. The researchers narrowed this ability to a small fragment of the protein. The...