When F-actin Becomes Too Much of a Good Thing

摘要

Tlymphocytes are highly mobile and long-lived cells that alternate between circulating in the blood and migrating rapidly in tissue in search of antigens. The actin cytoskeleton, the cell's diverse and dynamic infrastructure, plays a key role in thisprocess, and much attention has been focused on branched networks of filamentous actin (F-actin). These fibrous networks are generated through the activity of the actinrelated protein 2/3 (Arp2/3) complex. This complex forms F-actin structures that enable T cells to migrate (see the figure) and to forge a signaling synapse at the interface of an activated T cell and an antigen-presenting cell. Thus, F-actin has been viewed as a "good thing" that is necessary for cell motility and sustained cell signaling. On page 839 of this issue, Foger et al. (1) suggest that there can be too much of a good thing. Deficiency in the protein coronin-1, a natural antagonist of Arp2/3, increases F-actin content in a T cell, but in so doing it inhibits chemotactic responses and decreases mitochondrial membrane potential, leading to cell death. Surprisingly, loss of coronin-1 has no consequences for immunological synapse formation or T cell activation.