Assignment of the Dynamin-1 Gene (DNM1) to Human Chromosome 9q34 by Fluorescencein SituHybridization and Somatic Cell Hybrid Analysis

Newman-Smith, ED; Dl, Shurland; Bliek, AM van der

doi:10.1006/geno.1996.4596

Cited by 8 publications

(4 citation statements)

References 17 publications

(5 reference statements)

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“…Classical dynamins are the best-understood members of the DSF. In mammals, these are encoded by three different genes: DNM1, DNM2 and DNM3, located on chromosomes 9, 19 and 1, respectively [5][6][7]. Classical dynamins are composed of five highly conserved domains: an amino-terminal GTPase domain that binds and hydrolyses GTP, a middle structural domain, a PH-domain involved in lipid membrane interactions, a GTPase effector domain (GED), and an arginine-and proline-rich domain (PRD) that allows dynamin association with SH3-containing proteins [1,2,[8][9][10].…”

Section: Introductionmentioning

confidence: 99%

A centronuclear myopathy‐causing mutation in dynamin‐2 disrupts neuronal morphology and excitatory synaptic transmission in a murine model of the disease

Arriagada‐Diaz,

Flores‐Muñoz,

Gómez‐Soto

et al. 2023

Neuropathology Appl Neurobio

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AimsDynamin‐2 is a large GTPase, a member of the dynamin superfamily that regulates membrane remodelling and cytoskeleton dynamics. Mutations in the dynamin‐2 gene (DNM2) cause autosomal dominant centronuclear myopathy (CNM), a congenital neuromuscular disorder characterised by progressive weakness and atrophy of the skeletal muscles. Cognitive defects have been reported in some DNM2‐linked CNM patients suggesting that these mutations can also affect the central nervous system (CNS). Here we studied how a dynamin‐2 CNM‐causing mutation influences the CNS function.MethodsHeterozygous mice harbouring the p.R465W mutation in the dynamin–2 gene (HTZ), the most common causing autosomal dominant CNM, were used as disease model. We evaluated dendritic arborisation and spine density in hippocampal cultured neurons, analysed excitatory synaptic transmission by electrophysiological field recordings in hippocampal slices, and evaluated cognitive function by performing behavioural tests.ResultsHTZ hippocampal neurons exhibited reduced dendritic arborisation and lower spine density than WT neurons, which was reversed by transfecting an interference RNA against the dynamin‐2 mutant allele. Additionally, HTZ mice showed defective hippocampal excitatory synaptic transmission and reduced recognition memory compared to the WT condition.ConclusionOur findings suggest that the dynamin‐2 p.R465W mutation perturbs the synaptic and cognitive function in a CNM mouse model and support the idea that this GTPase plays a key role in regulating neuronal morphology and excitatory synaptic transmission in the hippocampus.

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Section: Introductionmentioning

confidence: 99%

A centronuclear myopathy‐causing mutation in dynamin‐2 disrupts neuronal morphology and excitatory synaptic transmission in a murine model of the disease

Arriagada‐Diaz,

Flores‐Muñoz,

Gómez‐Soto

et al. 2023

Neuropathology Appl Neurobio

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“…Classical dynamins are the best understood members of the DSF. In mammals, these are encoded by three different genes: DNM1, DNM2 and DNM3 located on chromosomes 9, 19 and 1, respectively (Newman-Smith, et al, 1997;Züchner, et al, 2005;Noakes, et al, 1999). Classical dynamins are composed by five highly conserved domains: an amino-terminal GTPase domain that binds and hydrolyze GTP, a middle structural domain, a PH-domain involved in lipid membrane interaction, a GTP-ase effector domain (GED) and an arginine-and proline-rich domain (PRD) that allows dynamin association with SH3-containing proteins (Praefcke, et al, 2004;Ferguson, et al, 2012;Antonny, et al, 2016;Singh, et al, 2017;Arriagada-Diaz, et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

A centronuclear myopathy-causing mutation in dynamin-2 perturbs the actin-dependent structure of dendritic spines leading to excitatory synaptic defects in a murine model of the disease

Arriagada-Diaz

Gómez

Prado-Vega

et al. 2021

Preprint

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Dynamin-2 is a large GTP-ase, member of the dynamin superfamily, that regulates membrane remodeling and cytoskeleton dynamics. In the mammalian nervous system dynamin-2 modulates synaptic vesicle (SV)-recycling at the nerve terminals and receptor-trafficking to and from postsynaptic densities (PSDs). Mutations in dynamin-2 cause autosomal dominant centronuclear myopathy (CNM), a congenital neuromuscular disorder characterized by progressive weakness and atrophy of distal skeletal muscles. Cognitive defects have also been reported in dynamin-2-linked CNM patients suggesting a concomitant impairment of the central nervous system. Here we addressed the mechanisms that lead to cognitive defects in dynamin-2-linked CNM using a knock-in mouse model that harbors the p.R465W mutation in dynamin-2, the most common causing CNM. Our results show that these mice exhibit reduced capability to learn and acquire spatial and recognition memory, impaired long-term potentiation of the excitatory synaptic strength and perturbed dendritic spine morphology, which seem to be associated with actin defects. Together, these data reveal for the first time that structural and functional synaptic defects underlie cognitive defects in the CNM context. In addition our results contribute to the still scarce knowledge about the importance of dynamin-2 at central synapses.

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“…In mammals, classical dynamins are encoded by three genes: DNM1, DNM2, and DNM3 located in chromosomes 9 (Newman-Smith and others 1997), 19 (Zuchner and others 2005), and 1 (Noakes and others 1999), respectively. These genes can be subjected to alternative splicing, producing each one from four to thirteen spliced variants (Cao and others 1998).…”

Section: Introductionmentioning

confidence: 99%

Dynamin Superfamily at Pre- and Postsynapses: Master Regulators of Synaptic Transmission and Plasticity in Health and Disease

et al. 2020

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Dynamin superfamily proteins (DSPs) comprise a large group of GTP-ases that orchestrate membrane fusion and fission, and cytoskeleton remodeling in different cell-types. At the central nervous system, they regulate synaptic vesicle recycling and signaling-receptor turnover, allowing the maintenance of synaptic transmission. In the presynapses, these GTP-ases control the recycling of synaptic vesicles influencing the size of the ready-releasable pool and the release of neurotransmitters from nerve terminals, whereas in the postsynapses, they are involved in AMPA-receptor trafficking to and from postsynaptic densities, supporting excitatory synaptic plasticity, and consequently learning and memory formation. In agreement with these relevant roles, an important number of neurological disorders are associated with mutations and/or dysfunction of these GTP-ases. Along the present review we discuss the importance of DSPs at synapses and their implication in different neuropathological contexts.

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Assignment of the Dynamin-1 Gene (DNM1) to Human Chromosome 9q34 by Fluorescencein SituHybridization and Somatic Cell Hybrid Analysis

Cited by 8 publications

References 17 publications

A centronuclear myopathy‐causing mutation in dynamin‐2 disrupts neuronal morphology and excitatory synaptic transmission in a murine model of the disease

A centronuclear myopathy‐causing mutation in dynamin‐2 disrupts neuronal morphology and excitatory synaptic transmission in a murine model of the disease

A centronuclear myopathy-causing mutation in dynamin-2 perturbs the actin-dependent structure of dendritic spines leading to excitatory synaptic defects in a murine model of the disease

Dynamin Superfamily at Pre- and Postsynapses: Master Regulators of Synaptic Transmission and Plasticity in Health and Disease

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