High impact information on Dnm1l

• Molecular manipulations of dynamin-like GTPases Drp1 and OPA1 that reduce dendritic mitochondria content lead to loss of synapses and dendritic spines, whereas increasing dendritic mitochondrial content or mitochondrial activity enhances the number and plasticity of spines and synapses [1].
• DLP1 is enriched in subcellular membrane fractions of cytoplasmic vesicles and endoplasmic reticulum [2].
• A novel dynamin-like protein associates with cytoplasmic vesicles and tubules of the endoplasmic reticulum in mammalian cells [2].
• Here, we have tested if novel dynamin-like proteins are expressed in mammalian cells to support vesicle trafficking processes at cytoplasmic sites distinct from the plasma membrane [2].
• These results suggest that hFis1 participates in mitochondrial fission through an interaction that recruits DLP1 from the cytosol [3].

Biological context of Dnm1l

• Point mutations in the GTP-binding domain of DLP1 (K38A and D231N) dramatically changed its intracellular distribution from punctate vesicular structures to either an aggregated or a diffuse pattern [4].
• How DLP1 might participate in the biogenesis of two presumably distinct organelle systems is discussed [4].
• Three rat brain alternative splicing dynamin-like protein variants: interaction with the glycogen synthase kinase 3beta and action as a substrate [5].
• Moreover, in vitro kinase (phosphorylation) assay showed that mammalian dynamin-like protein acts as a substrate for glycogen synthase kinase 3beta [5].
• In this report, three different alternatively spliced dynamin-like protein variants (DLP1-WT, -11, and -37) from rat brain were identified by reverse transcription/polymerase chain reaction (RT-PCR) [5].

Anatomical context of Dnm1l

• Consistent with these observations, electron microscopy of DLP1 mutant cells revealed a striking and quantitative change in the distribution and morphology of mitochondria and the ER [4].
• Mammalian dynamin-like protein DLP1 tubulates membranes [6].
• Furthermore, DLP1 has been shown to associate with punctate vesicles that are in intimate contact with microtubules and the endoplasmic reticulum (ER) in mammalian cells [4].
• A recently identified mammalian dynamin-like protein (DLP1) is essential for the proper cellular distribution of mitochondria and the endoplasmic reticulum in cultured cells [6].
• Dynamin-like protein, a large GTP-binding protein, has recently been cloned, and studies have shown that it may be involved in the formation of coated vesicles [5].

Associations of Dnm1l with chemical compounds

• In addition, immunoblot analysis revealed the presence of DLP1 in highly purified peroxisomal fractions from rat liver and an increase of DLP1 after treatment of rats with the peroxisome proliferator bezafibrate [7].

Other interactions of Dnm1l

• Transcript levels of gene products involved in mtDNA maintenance (Tfam), mitochondrial protein degradation (LON protease), fusion (fuzzy onion homolog), and fission (dynamin-like protein, synaptojanin-2alpha) were also unchanged [8].
• However, the side chains known to be functionally important in beta-defensin-12 and ShI are not conserved in DLP-1, suggesting that it has a different biological function [9].

Analytical, diagnostic and therapeutic context of Dnm1l

• Strikingly, cells expressing DLP1 mutants or microinjected with DLP1 antibodies showed a marked reduction in ER fluorescence and a significant aggregation and tubulation of mitochondria by immunofluorescence microscopy [4].
• We examined the interaction of these three rat brain dynamin-like protein variants with glycogen synthase kinase 3beta (Gsk-3beta) using the yeast two-hybrid screening, in vitro binding assay, and immunoprecipitation analysis [5].

References