dynamin

Dynamin is a family of large GTPases essential for membrane scission during clathrin-mediated endocytosis, catalyzing the release of vesicles from the plasma membrane through a GTP-dependent constriction mechanism.

In vertebrates, the dynamin family includes three main paralogs: dynamin-1 (DNM1), dynamin-2 (DNM2), and dynamin-3 (DNM3). They share a common domain organization: an N-terminal GTPase domain, followed by a middle (assembly) domain, a pleckstrin homology (PH) domain that binds phosphoinositides, a GTPase effector domain (GED) that modulates activity, and a C-terminal proline-rich domain (PRD) that engages SH3-domain-containing partner proteins.

Dynamin is recruited to the neck of budding vesicles at the plasma membrane through interactions with phosphoinositides and adaptor proteins such as amphiphysin, endophilin, and SNX9. It oligomerizes to form collar- or spiral-shaped structures around the vesicle neck. GTP hydrolysis triggers conformational changes that constrict and eventually sever the vesicle from the membrane, completing the fission step of endocytosis.

Regulation occurs via the GTP/GDP cycle and through interactions with accessory proteins and lipids; dynamin activity is coordinated with other endocytic steps. In neurons, dynamin-1 is particularly important for rapid synaptic vesicle recycling. Mutations in DNM1 or DNM2 are associated with neurological and muscular disorders, including centronuclear myopathy and Charcot–Marie–Tooth disease, respectively. Dynamin-related proteins, such as Drp1, perform related membrane-remodeling roles in other contexts, notably mitochondrial fission, highlighting the broader importance of this protein family. Dynamin is evolutionarily conserved across eukaryotes and remains a key regulator of membrane trafficking.