Disease relevance of DNM1

• Moreover, we show that internalization of PA is dynamin and Eps15 dependent, indicating that the clathrin-dependent pathway is the major route of anthrax toxin entry into the cell [1].
• Based on the FAP-1- and dynamin-dependent regulation of Fas translocation, we have created human melanoma lines with different levels of surface expression of Fas [2].
• Finally, dynamin is apparently not involved in the formation of phagocytic vesicles containing Chlamydia [3].
• Inducible expression of a dominant-negative mutant of dynamin in a CD4-positive HeLa cell line reduced HIV infection by 40 to 80% [4].
• Grb2 dominantly associates with dynamin II in human hepatocellular carcinoma HepG2 cells [5].

Psychiatry related information on DNM1

• In cortical neurons of Huntington's disease patients with early stage pathology, dynamin immunoreactivity accumulated in cytoplasmic bodies [6].
• Overexpression of dynamin is induced by chronic stimulation of mu- but not delta-opioid receptors: relationships with mu-related morphine dependence [7].
• The results show a similar down-regulation and desensitization of mu and delta binding sites, whereas an overexpression of dynamin occurred only with mu agonists, strongly suggesting the relevance of this up-regulation with the opiate dependence [7].
• Subjects were 33 abstinent SDIs receiving inpatient treatment and 19 non-SDI normal controls (NC) well-matched on age, sex, ethnicity, and VIQ, who were assessed using the Iowa Gambling Task (GT) and a delayed non-match to sample task (DNM): measures of decision making and working memory, respectively [8].

High impact information on DNM1

• Such cargo-regulated CCPs show delayed recruitment of dynamin and can undergo an abortive event in which clathrin coats separate from the plasma membrane without concomitant receptor endocytosis [9].
• Tyrosine phosphorylation of either TTP or dynamin prevents their interaction, pointing to a possible mechanism of exclusion of TTP from some CCP [10].
• The mechanoenzyme dynamin acts at the fission step, but, in this issue of Cell, suggest an additional role of dynamin in preparing membranes for fusion [11].
• Dynamin is believed to assemble around the necks of clathrin-coated pits and assist in pinching vesicles from the plasma membrane [12].
• Crystal structure at 2.2 A resolution of the pleckstrin homology domain from human dynamin [13].

Chemical compound and disease context of DNM1

• Using recombinant adenovirus expressing human and Xenopus GnRH-Rs we have explored the relationship between receptor internalization and mitogen-activated protein kinase signaling in HeLa cells with regulated tetracycline-controlled expression of wild-type or a dominant negative mutant (K44A) of dynamin [14].
• Ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway [15].
• This is the situation when DNMP is placed in the methotrexate binding site of Lactobacillus casei crystal structure [16].
• The long-term results of a therapeutic regimen for adult acute lymphoblastic leukemia (ALL) have been analysed with the main purpose to evaluate the impact of Daunorubicin (DNM) dosage given during the induction [17].

Biological context of DNM1

• Cortactin and dynamin are required for the clathrin-independent endocytosis of gammac cytokine receptor [18].
• Through its SH3 domain, endophilin bound to proline-rich domains (PRDs) in other endocytic proteins, including synaptojanin and dynamin [19].
• Novel data point more clearly than ever towards a role for this protein in the actin cytoskeleton, mitogen-activated protein kinase signaling and apoptosis, suggesting that dynamin might be a signaling GTPase [20].
• Tyrosine phosphorylation of dynamin is markedly enhanced upon IL-5 stimulation [21].
• Unlike most GTPases, dynamin has a low affinity for nucleotide, a high rate of GTP hydrolysis, and can self-assemble, forming higher order structures such as rings and spirals that exhibit up to 100-fold stimulated GTPase activity [22].

Anatomical context of DNM1

• To further characterize the function of dynamin in clathrin-independent endocytosis, in particular its connection with the actin cytoskeleton, we focused on dynamin-binding proteins that interact with F-actin [18].
• At endocytic sites, dynamin may couple the fission reaction to the polymerization of an actin pool that functions in the separation of the endocytic vesicles from the plasma membrane [23].
• These findings suggest that dynamin is part of a protein network that controls nucleation of actin from membranes [23].
• In PIPK-induced tails, dynamin is further enriched at the interface between the tails and the moving organelles [23].
• It has been demonstrated that the amphiphysins also bind to clathrin, and we have proposed that this interaction may help to target synaptojanin and dynamin to sites of synaptic vesicle endocytosis [24].

Associations of DNM1 with chemical compounds

• Although dynamin localization to the tails required its proline-rich domain, expression of a dynamin mutant lacking this domain also diminished tail formation [23].
• Dynamin GTPase activity is essential for its fission activity, and it is stimulated by self-assembly as well as by interacting with its binding partners, such as microtubules, SH3 domain containing proteins, or inositol phospholipids [25].
• We describe here in detail the procedure of the dynamin GTPase assay and the results demonstrating stimulatory effect of amphiphysin on dynamin GTPase activity, which is highly dependent on the liposome size [25].
• Nitric oxide regulates endocytosis by S-nitrosylation of dynamin [26].
• We report that dynamin, which interacts with NO synthase, is S-nitrosylated at a single cysteine residue (C607) after stimulation of the beta(2) adrenergic receptor [26].

Physical interactions of DNM1

• SNX9 binds directly to both dynamin-1 and dynamin-2 [27].
• We therefore propose a model where degranulated serglycin-bound granzymes require dynamin for uptake [28].
• Amphiphysin is an SH3 domain-containing neuronal protein that is highly concentrated in nerve terminals where it interacts via its SH3 domain with dynamin I, a GTPase implicated in synaptic vesicle endocytosis [29].
• Furthermore, using high resolution NMR spectroscopy, we have identified amino acid residues on Sumo-1 that directly interact with the GED of dynamin [30].
• Dynamin interacts with a number of partners such as endophilin and proteins involved in coordination of endocytosis with motor molecules [31].

Co-localisations of DNM1

• LPS was endocytosed by a receptor-mediated mechanism dependent on dynamin and clathrin and colocalized with TLR4 on early/sorting endosomes [32].

Regulatory relationships of DNM1

• Dynamin GTPase is stimulated by crosslinking through the C-terminal proline-rich domain [33].
• SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis [27].
• Moreover, expression of Y231F/Y597F dynamin inhibits beta2-AR internalization and the isoproterenol-stimulated mitogen-activated protein kinase activation [34].
• Internalization and desensitization of the oxytocin receptor is inhibited by Dynamin and clathrin mutants in human embryonic kidney 293 cells [35].
• Notably, the antibody displaces a fraction of the Golgi-bound dynamin II indicating that profilin I may indirectly promote vesicle formation by supporting the binding of dynamin II to the Golgi membrane [36].

Other interactions of DNM1

• Amphiphysin I and II are nerve terminal-enriched proteins that display src homology 3 domain-mediated interactions with dynamin and synaptojanin [24].
• Hudy-2 binds to an epitope within amino acids 822-838 that is common to dynamin-1 and dynamin-2 [33].
• Dynamin associates with a variety of SH3 domain-containing molecules via a C-terminal proline-rich motif and takes part, with them, in endocytic processes [37].
• These findings suggest that PLD, functioning as an intermolecular GAP for dynamin, accelerates EGFR endocytosis [38].
• First, we show that L. monocytogenes colocalizes with Met, EEA1, Cbl, clathrin and dynamin during entry [39].

Analytical, diagnostic and therapeutic context of DNM1

• Immunoprecipitations confirmed that both dynamin and SNAP-25 are complexed to EHSH1 in brain [40].
• Moreover, exposure of cells to the hormone leads to co-immunoprecipitation of dynamin with Shc and with insulin receptor [41].
• In addition, clathrin and dynamin in a complex with Amph were captured in the precipitate formed by mAbs and identified by the Western blot analysis [42].
• Microinjection of amphiphysin's SH3 domain or of a dynamin peptide containing the SH3 binding site inhibited synaptic vesicle endocytosis at the stage of invaginated clathrin-coated pits, which resulted in an activity-dependent distortion of the synaptic architecture and a depression of transmitter release [43].
• When the protein sheath is dynamin, it is commonly assumed that scission is brought about by the constriction of the sheath [44].

References