Does clathrin pull the fission trigger?

Clathrin-mediated vesicle budding is essential for a variety of intracellular membrane transport reactions in the secretory and endocytic pathways (1, 2). This process can be dissected in several sequential steps that include the recruitment of the clathrin coat, membrane invagination and concomitant propagation of the clathrin lattice, constriction of the vesicle neck, and finally fission of the coated vesicle, followed by its rapid uncoating (1, 3, 4). Although clathrin and clathrin adaptors, assisted by other accessory factors, drive this reaction up to the stage of a deeply invaginated coated pit, a distinct factor, the GTPase dynamin, is thought to play a critical role in fission (5, 6). To provide new clues concerning all sites where clathrin functions in mammalian cell physiology and on the vesicular traffic pathways that are dependent on clathrin, Iversen et al. (7) have engineered a mammalian cell line in which expression of clathrin can be suppressed by an inducible antisense RNA. Unexpectedly, this study has suggested a role for clathrin heavy chain in the regulation of dynamin expression and function.

This study suggests a role for clathrin heavy chain in the regulation of dynamin expression and function.

Whereas the use of genetics has significantly advanced the understanding of clathrin function in unicellular organisms (8, 9), perturbation of clathrin-mediated transport in mammalian cells has so far relied on indirect approaches. A first approach consisted of the overexpression of dominant negative mutants of dynamin that block clathrin-mediated endocytosis by producing an arrest of the fission reaction (5, 6). However, several considerations complicate the interpretation of these experiments. First, it was discovered that dynamin can function in clathrin independent pathways of endocytosis, including internalization via caveolae (10–15). Second, it remains controversial whether dynamin is absolutely required in all clathrin-dependent transport reactions, …