Dynamin 2 (DNM2) (DNM2)

Dynamin 2 (DNM2) is a ubiquitously expressed large GTPase that serves as a master regulator of membrane remodeling and vesicle scission in eukaryotic cells [1, 3]. It is primarily known for its role in clathrin-mediated and clathrin-independent endocytosis, where it self-assembles into helical polymers around the necks of budding vesicles and utilizes the energy from GTP hydrolysis to catalyze membrane fission [6, 11]. Beyond its role at the plasma membrane, DNM2 is involved in intracellular trafficking from the Golgi apparatus, exocytosis, and the organization of both the actin and microtubule cytoskeletons [3, 16]. Mutations in the DNM2 gene are the primary cause of several hereditary neuromuscular disorders, such as autosomal dominant centronuclear myopathy (CNM) and Charcot-Marie-Tooth disease (CMT), often through gain-of-function mechanisms that lead to hyperactive or overly stable dynamin polymers [1, 17]. In the context of oncology, DNM2 is frequently overexpressed in various cancers, where it promotes tumor cell migration, invasion, and proliferation by modulating signaling pathways and the actomyosin cytoskeleton [14, 18]. Consequently, DNM2 has emerged as a significant therapeutic target, with strategies ranging from small molecule inhibitors like Dynasore and its derivatives to antisense oligonucleotides designed to reduce its expression in disease states [9, 10]. However, because DNM2 is essential for many fundamental cellular processes and is expressed throughout the body, developing selective therapies that minimize systemic toxicity remains a major challenge [12, 16].

Other names

DNM2Dynamin IIDYN2DYNIICMT2MCMTDI1CMTDIBDI-CMTBLCCS5

Dynamin 2 inhibitors primarily function by binding to the GTPase domain to prevent GTP hydrolysis, which is essential for membrane scission, or by targeting the pleckstrin homology (PH) domain to block recruitment to the plasma membrane [4, 12]. Some inhibitors also interfere with the self-assembly of dynamin into helical polymers, thereby preventing the mechanical constriction of the vesicle neck [4, 10].