Redundant and distinct functions for dynamin-1 and dynamin-2 isoforms

A role for dynamin in clathrin-mediated endocytosis is now well established . However, mammals express three closely related, tissue-specific dynamin i soforms, each with multiple splice variants. Thus, an important question is whether these isoforms and splice variants function in vesicle formation f rom distinct intracellular organelles. There are conflicting data as to a r ole for dynamin-2 in vesicle budding from the TGN. To resolve this issue, w e compared the effects of over expression of dominant-negative mutants of d ynamin-1 (the neuronal isoform) and dynamin-2 (the ubiquitously expressed i soform) on endocytic and biosynthetic membrane trafficking in HeLa cells an d polarized MDCK cells. Both dyn1(K44A) and dyn2(K44A.) were potent inhibit ors of receptor-mediated endocytosis; however neither mutant directly affec ted other membrane trafficking events, including transport mediated by four distinct classes of vesicles budding from the TGN. Dyn2(K44A) more potentl y inhibited receptor-mediated endocytosis than dyn1(K44A) in HeLa cells and at the basolateral surface of MDCK cells. In contrast, dyn1(K44A) more pot ently inhibited endocytosis at the apical surface of MDCK cells. The two dy namin isoforms have redundant functions in endocytic vesicle formation, but can be targeted to and function differentially at subdomains of the plasma membrane.