dynamin1

Dynamin-1 is a large GTPase in the dynamin family, encoded by the DNM1 gene and primarily expressed in neurons. It plays a central role in clathrin-mediated endocytosis and synaptic vesicle recycling by mediating the scission of vesicles from the plasma membrane after neurotransmitter release. Dynamin-1 is one of several dynamin isoforms, with dynamin-2 being ubiquitously expressed and dynamin-3 enriched in brain and testis.

The protein has a modular architecture that supports its function. It contains an N-terminal GTPase domain, a middle (stalk) domain, a GTPase effector domain (GED), a pleckstrin homology (PH) domain that binds phosphoinositides at the plasma membrane, and a C-terminal proline-rich domain (PRD) that mediates interactions with SH3-domain-containing proteins. The GED promotes self-assembly and stimulates GTPase activity, enabling dynamin-1 to form collar-like polymers around vesicle necks.

Mechanistically, dynamin-1 oligomerizes at sites of endocytosis and constricts the neck of budding vesicles in a process driven by GTP binding and hydrolysis, ultimately facilitating membrane scission. Its activity is coordinated with clathrin coats and adaptor proteins, and is regulated by interactions through the PRD and by cellular phosphorylation states.

Regulation and significance: dynamin-1 expression is highest in neurons and its activity is modulated by phosphorylation and dephosphorylation events in response to neuronal activity. Mutations in DNM1 have been linked to epileptic encephalopathy and other neurodevelopmental disorders, underscoring its essential role in efficient synaptic vesicle recycling and neurotransmission.