ABSTRACTDynamins are large cytoplasmic GTPases that are targeted to specific cellular membranes which they remodel via membrane fusion or fission. Although the mechanism of target membrane selection by dynamins has been studied, the molecular basis of conferring specificity to bind specific lipids on the target membranes is not known in any of the family members. Here, we report a mechanism of nuclear membrane recruitment of Drp6 that is involved in nuclear remodeling in Tetrahymena thermophila. Recruitment of Drp6 depends on a domain that binds to cardiolipin-rich bilayers. Consistent with this, the nuclear localization of wildtype Drp6 was inhibited by depleting cardiolipin in the cell. Cardiolipin binding was blocked with a single amino acid substitution (I553M) in the membrane-binding domain of Drp6. Importantly, the I553M substitution was sufficient to block nuclear localization without affecting other properties of Drp6. Consistent with this result, co-expression of wildtype Drp6 was sufficient to rescue the localization defect of I553M variant in Tetrahymena. Inhibition of cardiolipin synthesis or perturbation in Drp6 recruitment to nuclear membrane caused defects in the formation of new macronuclei post-conjugation. Taken together, our results elucidate a molecular basis of target membrane selection by a nuclear dynamin, and establish the importance of a defined membrane-binding domain and its target lipid in facilitating nuclear expansion.
Molecular Basis for Lipid Specificity of the Coagulation Factor X Membrane-Binding Domain
