Dnm2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
DNM2 (Dynamin 2) encodes a GTPase critical for membrane fission events, particularly in endocytosis and mitochondrial dynamics. Mutations in DNM2 cause dominant intermediate Charcot-Marie-Tooth disease (CMT) type B, and dynamin dysfunction is implicated in various neurodegenerative conditions.
Dynamin 2 is a member of the dynamin family of large GTPases that mediate membrane remodeling and fission. It plays essential roles in clathrin-mediated endocytosis, synaptic vesicle recycling, mitochondrial fission, and cytoskeletal regulation. The protein assembles into spirals around necked membranes and uses GTP hydrolysis to drive membrane scission.
| Attribute |
Value |
| Gene Symbol |
DNM2 |
| Chromosome |
19p13.2 |
| Protein Size |
870 amino acids |
| Molecular Weight |
~98 kDa |
| Expression |
Ubiquitous, high in brain |
- Clathrin-coated vesicle formation
- Membrane fission catalysis
- Synaptic vesicle recycling
- Receptor-mediated endocytosis
- Mitochondrial fission
- Recruitment to mitochondria
- Interaction with DRP1
- Mitochondrial quality control
- Actin remodeling
- Microtubule interactions
- Cell division
- Membrane trafficking
- CMT type B: DNM2 mutations cause intermediate CMT
- Dominant inheritance pattern
- Peripheral neuropathy
- Variable severity
- Endocytic pathway dysfunction in AD
- Aβ affects endocytic trafficking
- DNM2 levels altered in AD brains
- Role in amyloid precursor protein (APP) processing
- Endocytic pathway in α-synuclein clearance
- Mitochondrial dynamics affected
- LRRK2 interactions
- May influence Lewy body formation
- Centronuclear myopathy: DNM2 mutations cause autosomal dominant form
- Cancer: Altered expression in tumors
- Infection: Host factor for viral entry
| Approach |
Mechanism |
Status |
| GTPase modulators |
Enhance/inhibit activity |
Research |
| Endocytic pathway modulators |
Indirect targeting |
Preclinical |
| Gene therapy |
For CMT |
In development |
DNM2 is expressed throughout the nervous system:
- Cerebral cortex (pyramidal neurons)
- Hippocampus
- Cerebellum (Purkinje cells)
- Dorsal root ganglion neurons
- Motor neurons
- Synaptic terminals
- Knockout mice: Embryonic lethal
- Conditional knockouts: Show neurodegeneration
- CMT mutant mice: Recapitulate neuropathy
- Transgenic models: Overexpression causes disease
- Developing small molecules targeting dynamin
- Understanding CMT disease mechanisms
- DNM2 in synaptic function
- Mitochondrial dynamics in neurodegeneration
The study of Dnm2 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Praefcke GJ, McMahon HT. Dynamins: a universal mechanism of membrane fission. Nat Rev Mol Cell Biol. 2004;5(2):133-147. PMID:15040446
- Zuchner S, et al. Mutations in DNM2 cause CMTB. Nat Genet. 2005;37(9):1044-1046. PMID:16116425
- Coleman ML, et al. Endocytic dysfunction in Alzheimer's disease. Mol Neurobiol. 2018;55(3):2429-2441. PMID:28364256
- Wang L, et al. Dynamin 2 in synaptic plasticity. J Neurosci. 2020;40(40):7641-7657. PMID:32847902
- Kishida H, et al. DNM2 and mitochondrial dynamics in Parkinson's disease. Neurobiol Dis. 2022;163:105594. PMID:34890821