DNM1
GeneName
DNM1
Summary
DNM1, also known as dynamin or dynamin-1, is a 97 kDa GTPase that plays a pivotal role in membrane dynamics, particularly in the processes of endocytosis and vesicle trafficking. It is primarily localised to the cytoplasm and various membrane structures, including clathrin-coated pits, presynaptic sites, and endocytic vesicles. DNM1 is essential for the scission of newly formed vesicles from the plasma membrane, facilitating receptor internalisation and synaptic vesicle recycling. It functions through its ability to bind GTP and undergo conformational changes that drive membrane fission, and it can also interact with phosphoinositides and microtubules, enhancing its functional versatility in cellular processes.
Importance
DNM1 is relevant to: - Understanding synaptic transmission and plasticity due to its role in synaptic vesicle recycling and neurotransmitter release - Investigating neurodegenerative diseases where endocytic dysfunction may contribute to pathology - Exploring cancer biology, as alterations in endocytosis can affect receptor signalling and cellular uptake of therapeutic agents - Studying metabolic disorders linked to vesicle trafficking and membrane dynamics
Top Products
For researchers investigating DNM1, we highly recommend the top-selling recombinant antibody, Anti-Dynamin 1 antibody [EP801Y] (ab52611). This antibody has been validated in knockout models, ensuring its reliability in experimental settings. It is suitable for a variety of applications, with a particular emphasis on Western blotting (WB) and immunohistochemistry (IHC). With 16 citations, this antibody is gaining recognition in the research community for its effectiveness in detecting Dynamin 1. Its recombinant nature guarantees batch-to-batch consistency, making it an excellent choice for your studies.
Abcam Product Citation Summary
The use of the Abcam antibody ab52611 for detecting DNM1 in rat brain lysates highlights its relevance in studies focused on synaptic protein expression, which is crucial for understanding neuronal function and communication.
Abcam Product Citation Table
Domain
The dynamin-type G mediates homodimerization and plays a role in self-assembly.
The C-terminal proline-rich domain (PRD) mediates interaction with SH3-binding partners (By similarity). Is required for DNM1 self-assembly (PubMed:7877694).
The PH domain binds phosphoinositides such as 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate, 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate and 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate, and mediates receptor-mediated endocytosis.
Function
Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission and participates in many forms of endocytosis, such as clathrin-mediated endocytosis or synaptic vesicle endocytosis as well as rapid endocytosis (RE) (PubMed:15703209, PubMed:20428113, PubMed:29668686, PubMed:8101525, PubMed:8910402, PubMed:9362482). Associates to the membrane, through lipid binding, and self-assembles into rings and stacks of interconnected rings through oligomerization to form a helical polymer around the vesicle membrane leading to constriction of invaginated coated pits around their necks (PubMed:30069048, PubMed:7877694, PubMed:9922133). Self-assembly of the helical polymer induces membrane tubules narrowing until the polymer reaches a length sufficient to trigger GTP hydrolysis (PubMed:19084269). Depending on the curvature imposed on the tubules, membrane detachment from the helical polymer upon GTP hydrolysis can cause spontaneous hemifission followed by complete fission (PubMed:19084269). May play a role in regulating early stages of clathrin-mediated endocytosis in non-neuronal cells through its activation by dephosphorylation via the signaling downstream of EGFR (PubMed:29668686). Controls vesicle size at a step before fission, during formation of membrane pits, at hippocampal synapses (By similarity). Controls plastic adaptation of the synaptic vesicle recycling machinery to high levels of activity (By similarity). Mediates rapid endocytosis (RE), a Ca(2+)-dependent and clathrin- and K(+)-independent process in chromaffin cells (By similarity). Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP (By similarity). Through its interaction with DNAJC6, acts during the early steps of clathrin-coated vesicle (CCV) formation (PubMed:12791276).
Involvement in disease
Developmental and epileptic encephalopathy 31A
DEE31A
An autosomal dominant epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent.
None
The disease is caused by variants affecting the gene represented in this entry.
Developmental and epileptic encephalopathy 31B
DEE31B
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE31B is an autosomal recessive form with onset in the first months of life.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation at Ser-774 by GSK3B/GSK3-beta leads to inactivation of receptor-mediated endocytosis in non-neuronal cells (PubMed:29668686). Dephosphorylation at Ser-774, through the EGFR downstream signaling, leads to activation and regulates early stages of clathrin-mediated endocytosis (CME) (PubMed:29668686). Phosphorylated by CDK5 leading to synaptic vesicle endocytosis (SVE) activation (By similarity).
Sequence Similarities
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.
Cellular localization
- Cell membrane
- Membrane
- Clathrin-coated pit
- Cytoplasmic vesicle
- Presynapse
- Cytoplasmic vesicle
- Secretory vesicle
- Chromaffin granule
- Associated to the membrane in a helical polymer shape in a GTP bound state (PubMed:30069048). Transiently recruited to endocytic clathrin-coated pits (CCPs) at a late stage of clathrin-coated vesicle (CCV) formation (PubMed:15703209).
Alternative names
DNM, DNM1, Dynamin-1, Dynamin, Dynamin I