Self-Assembly Precedes Target Membrane Recruitment of a Nuclear Dynamin-Related Protein.

Dynamin family proteins typically do not depend on higher-order oligomerization; instead, dimerization and/or tetramerization is sufficient for their target membrane recruitment. Here, we demonstrate that dimerization/tetramerization alone is not enough, but self-assembly into a higher-order structure is also required for targeting a dynamin-related protein, dynamin-related protein 6 (Drp6), to the nuclear membrane. We identify residues 411-GKFR-414 as important for higher-order oligomerization of Drp6 but dispensable for its dimerization/tetramerization. Furthermore, while the mutation of GKFR residues does not affect membrane-binding ability in vitro, it inhibits the nuclear localization of Drp6 in vivo. Ultrastructure expansion microscopy and fast super-resolution live cell imaging demonstrate that the cytosolic, higher-order self-assembled structure of Drp6 is recruited to the nuclear envelope. These findings establish self-assembly into a higher-order oligomer as a prerequisite for target membrane recruitment of a dynamin-related protein.