DNM1

Description

The DNM1 (dynamin 1) is a protein-coding gene located on chromosome 9.

Dynamin-1 is a protein encoded by the DNM1 gene in humans. It possesses unique mechanochemical properties that enable membrane tubulation and severing, playing a vital role in clathrin-mediated endocytosis and other vesicular trafficking processes. Dynamin interacts with actin and other cytoskeletal proteins and can self-assemble, stimulating GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, especially on chromosomes Y and 15. Various isoforms are produced through alternative splicing. Mutations in DNM1 have been linked to a severe childhood epilepsy called developmental and epileptic encephalopathy. Most pathogenic variants are missense variants, impairing synaptic vesicle endocytosis in a dominant negative manner.

DNM1, also known as Dynamin, Dynamin I, catalyzes the hydrolysis of GTP, using this energy to mediate vesicle scission. It participates in various forms of endocytosis, including clathrin-mediated endocytosis, synaptic vesicle endocytosis, and rapid endocytosis. DNM1 binds to the membrane through lipid interactions and self-assembles into rings and interconnected ring stacks, forming a helical polymer around the vesicle membrane, which constricts invaginated coated pits at their necks. This helical polymer's self-assembly induces membrane tubule narrowing until it reaches a length that triggers GTP hydrolysis. Depending on the curvature of the tubules, membrane detachment from the polymer after GTP hydrolysis can lead to spontaneous hemifission followed by complete fission. DNM1 might also regulate early stages of clathrin-mediated endocytosis in non-neuronal cells by activating through dephosphorylation downstream of EGFR signaling. It controls vesicle size during membrane pit formation at hippocampal synapses and adapts the synaptic vesicle recycling machinery to high activity levels. DNM1 mediates rapid endocytosis, a Ca(2+)-dependent and clathrin- and K(+)-independent process in chromaffin cells. It acts as a microtubule-associated force-producing protein, forming microtubule bundles and binding and hydrolyzing GTP. Through its interaction with DNAJC6, DNM1 plays a role in the early stages of clathrin-coated vesicle (CCV) formation.

DNM1 is also known as DEE31, DEE31A, DEE31B, DNM, EIEE31.

Associated Diseases

• Non-specific early-onset epileptic encephalopathy
• Epileptic encephalopathy, early infantile, 31
• Developmental and epileptic encephalopathy 31B, autosomal recessive
• Lennox-Gastaut syndrome