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The twin siblings exhibit mild to moderate intellectual disability and autistic symptoms but no epileptic encephalopathy. Exome sequencing revealed a genetic variant, c.1603A>G (p.Lys535Glu), in the PH domain of dynamin 1. The twin sisters studied here share the de novo variant, c.1603A>G (p.Lys535Glu) in exon 15 of DNM1, classified as likely pathogenic.
The data show that the dynamin-amphiphysin helices are rearranged to form clusters upon GTP hydrolysis and membrane constriction occurs at protein-uncoated regions flanking the clusters.
Together, these observations suggest that while endophilin helps shape endocytic tubules and recruit dynamin to endocytic sites, it can also block membrane fission when present in excess by inhibiting inter-dynamin interactions.
The authors show that in fibroblasts, dynamin GTP hydrolysis occurs as stochastic bursts, which are randomly distributed relatively to the peak of dynamin assembly. Thus, dynamin disassembly is not coupled to GTPase activity, supporting that the GTP energy is primarily spent in constriction.
Dynamin isoforms differentially regulate the endocytosis and apoptotic signaling downstream of TRAIL-death receptor (TRAIL-DR) complexes in cancer cells. TRAIL stimulation activates ryanodine receptor-mediated calcium release from endoplasmic reticulum stores, leading to calcineurin-mediated dephosphorylation and activation of Dyn1, TRAIL-DR endocytosis, and increased resistance to TRAIL-induced apoptosis.
Three genes in our epilepsy cohort (COQ4, DNM1, and PURA), accounting for 14% (3/21) of all novel genetic etiologies identified in patients with epilepsy, were subsequently confirmed in independent publications.
Study delineates the phenotypic spectrum of DNM1 encephalopathy, an emerging disease of synaptic vesicle fission characterized by severe to profound developmental delay, infantile-onset epilepsy beginning with infantile spasms, and movement disorder. The genetic landscape of DNM1 encephalopathy is notable for the recurrent c.709C>T (p.Arg237Trp) variant and localization of mutations to specific domains of the protein.
CLCb/Dyn1-dependent adaptive clathrin-mediated endocytosis selectively altered EGF receptor trafficking.
interation of DG with laminin and dynamin is involved in the regulation of AQP4 internalization
Down-regulation of Dyn1 activity enhances extracellular Nme1 in human colon tumor cell lines.
Hypoxic down-regulation of constitutive endocytosis is HIF-independent, and involves caveolin-1-mediated inhibition of dynamin-dependent, membrane raft endocytosis.
study reports 2 patients with early onset epileptic encephalopathy possessing de novo DNM1 mutations; detected the novel mutation c.127G>A (p.Gly43Ser) in a patient with Lennox-Gastaut syndrome, and a recurrent mutation c.709C>T (p.Arg237Trp) in a patient with West syndrome
The rare variants in DNM1 were significantly associated with smoking status.
Data indicate that stimulation of the dynamin GTPase activity by SH3 domains is determined by its middle domain.
molecular simulations corroborate the bimodal character of dynamin action and indicate radial and axial forces as dominant, although not independent, drivers of hemi-fission and fission membrane- transformations, respectively
Data indicate the dynamics of a dynamin 1-catalysed GTP hydrolysis and tube-severing reaction in real time using fluorescence microscopy.
This study identified and confirmed DNM1 protein changes within the postsynaptic density in schizophrenia.
findings support a role for HTT on dynamin 1 function and ER homoeostasis. Proteolysis-induced alteration of this function may be relevant to disease.
CRISPR-Cas9n-mediated knockout and reconstitution studies establish that dynamin-1 is activated by Akt/GSK3beta signaling in H1299 non-small lung cancer cells.
Data suggest that by binding to both clathrin and F-actin, mammalian actin-binding protein 1 (mAbp1; HIP-55 or SH3P7) is specifically recruited at a late stage of clathrin-coated pits (CCPs) formation, which subsequently recruits dynamin to CCPs.
dynamin is a molecular motor which would be involved in GLUT4 translocation by facilitating exocytosis
reveal functional differences between Dnm1a and Dnm1b isoforms in the presence of a challenge, i.e. toxic Dnm1(Ftfl), while reinforcing its effect explicitly in this model of severe pediatric epilepsy
in the mature epididymis, predominantly localized in clear cells of the distal segments
Dynamin may facilitate Fas-mediated apoptotic death in the brain, and Hsp70 may protect by preventing this trafficking.
These results suggested that dynamin 1 was susceptible to the aging process, and that a reduction in dynamin 1 may result in hippocampaldependent memory deficits by disrupting endocytosis and the release of neurotransmitters.
Tissue-specific dynamin-1 deletion at the calyx of Held decreases short-term depression through a mechanism distinct from vesicle resupply.
the identification of the oligomerization cycle of dynamin is an attractive potential therapeutic target to treat chronic kidney diseases .
In the developing neurons, there is a dynamin 1-, dynamin 3- and clathrin-independent pathway of synaptic vesicle recycling mediated by bulk endocytosis.
Using an inducible knockout mouse model to generate dynamin 1- and 2-deficient primary osteoclast precursors and myoblasts, it was shown that fusion of both cell types requires dynamin.
Dynamin 1 is required for memory formation.
As low-level expression of the dynamin 3 gene in these cells could not be excluded, we have now engineered dynamin 1, 2 and 3 triple KO (TKO) fibroblasts.
Results further implicate dynamin-1 in vesicular protein transport processes relevant to synaptic and post-Golgi pathways and indicate a possible role in photoreceptor stability
Data indicate that coxsackievirus and adenovirus receptor (CAR) internalization was lipid microdomain-, actin-, and dynamin-dependent, and subsequently followed by CAR degradation in lysosomes.
A missense mutation of dynamin 1 inhibits endocytosis via clathrin-mediated endocytosis.
Data indicate that dynamin, clathrin, adaptor protein complex-2 (AP2), and amphiphysin contribute to the depolarization-evoked entry in endocytosis.
Data show that dynamin 1 and dynamin 2 GTPases localize to the developing acrosome of maturing germ cells.
S857 phosphorylation of dynamin 1 is modulated by neuronal activity in nerve terminals.
Analysis of cysteine string protein alpha (CSPalpha)-dynamin 1 interactions reveals unexpectedly that CSPalpha regulates the polymerization of dynamin 1 in mouse hippocampal cell cultures.
These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis.
Equine herpesvirus type 1 pUL56-induced MHC-I endocytosis required dynamin and tyrosine kinase but was independent of clathrin and caveolin-1, the main constituents of the clathrin- and raft/caveola-mediated endocytosis pathways, respectively.
This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described.
, dynamin, brain
, dynamin 1