Limits...
Cytoplasmic dynein heavy chain: the servant of many masters.

Schiavo G, Greensmith L, Hafezparast M, Fisher EM - Trends Neurosci. (2013)

Bottom Line: This complex comprises different subunits assembled on a cytoplasmic dynein heavy chain 1 (DYNC1H1) dimer.Cytoplasmic dynein is particularly important for neurons because it carries essential signals and organelles from distal sites to the cell body.Additionally, several DYNC1H1 mutations have recently been found in human patients that give rise to a broad spectrum of developmental and midlife-onset disorders.

View Article: PubMed Central - PubMed

Affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, National Hospital for Neurology and Neurosurgery, University College London, Queen Square, London WC1N 3BG, UK; Molecular NeuroPathobiology, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Electronic address: giampietro.schiavo@ucl.ac.uk.

Show MeSH

Related in: MedlinePlus

The cytoplasmic dynein complex. (A) Diagram of the cytoplasmic dynein motor complex including the heavy chain (HC) dimer and its associated subunits. A model of the motor domain [5] built from yeast cytoplasmic dynein (PDB ID 4AKG) and the mouse microtubule-binding domain (MTBD) (PDB ID 3ERR) assembled by Dr A.P. Carter has been overlapped with the schematic of the dynein HC in its apo or post-power stroke form [5,93,94]. Adapted, with permission, from The Company of Biologists (J. Cell Sci. 126, 705–713; [4]). The electron micrograph of an isolated molecule of monomeric dynein from Chlamydomonas reinhardtii flagella in its pre-power stroke form is shown for comparison on the right. Adapted with permission from Macmillan Publishers (Nature 421, 715–718; [93]). Conformational changes driven by ATP hydrolysis in the motor domain, which alter the relative position of the stem and the tail/linker, are hypothesised to lead to the power stroke and progression on microtubules [5,94]. The HCs (in dark violet) contain the six AAA ATPase domains (in red), the stalk region, which includes the MTBD (in dark yellow and yellow, respectively), the buttress (in orange), and the linker region. HCs are associated with light intermediate chains (LICs) (in green), intermediate chains (ICs) (in cyan), and light chains (LCs) (in light yellow). (B) Domain composition of the cytoplasmic dynein HC. In addition to the functional domains shown in (A), this scheme displays the homodimerisation region and linker (in white). The positions on the dynein HC of the three mouse mutations (Loa, Legs at odd angles; Cra, Cramping 1; Swl, Sprawling; bottom) and the human mutations discussed in this review (top) are indicated.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3824068&req=5

fig0005: The cytoplasmic dynein complex. (A) Diagram of the cytoplasmic dynein motor complex including the heavy chain (HC) dimer and its associated subunits. A model of the motor domain [5] built from yeast cytoplasmic dynein (PDB ID 4AKG) and the mouse microtubule-binding domain (MTBD) (PDB ID 3ERR) assembled by Dr A.P. Carter has been overlapped with the schematic of the dynein HC in its apo or post-power stroke form [5,93,94]. Adapted, with permission, from The Company of Biologists (J. Cell Sci. 126, 705–713; [4]). The electron micrograph of an isolated molecule of monomeric dynein from Chlamydomonas reinhardtii flagella in its pre-power stroke form is shown for comparison on the right. Adapted with permission from Macmillan Publishers (Nature 421, 715–718; [93]). Conformational changes driven by ATP hydrolysis in the motor domain, which alter the relative position of the stem and the tail/linker, are hypothesised to lead to the power stroke and progression on microtubules [5,94]. The HCs (in dark violet) contain the six AAA ATPase domains (in red), the stalk region, which includes the MTBD (in dark yellow and yellow, respectively), the buttress (in orange), and the linker region. HCs are associated with light intermediate chains (LICs) (in green), intermediate chains (ICs) (in cyan), and light chains (LCs) (in light yellow). (B) Domain composition of the cytoplasmic dynein HC. In addition to the functional domains shown in (A), this scheme displays the homodimerisation region and linker (in white). The positions on the dynein HC of the three mouse mutations (Loa, Legs at odd angles; Cra, Cramping 1; Swl, Sprawling; bottom) and the human mutations discussed in this review (top) are indicated.

Mentions: Cytoplasmic dynein 1 is a large (∼1.5 MDa), multisubunit motor complex (Figure 1A) that moves towards the minus end of microtubules in eukaryotic cells [1]. It belongs together with the axonemal dyneins and cytoplasmic dynein 2 to the dynein superfamily. Axonemal dyneins are responsible for the movement of cilia and flagella, whereas cytoplasmic dynein 2 has a role in intraflagellar transport and is required for cilia and flagella assembly [1].


Cytoplasmic dynein heavy chain: the servant of many masters.

Schiavo G, Greensmith L, Hafezparast M, Fisher EM - Trends Neurosci. (2013)

The cytoplasmic dynein complex. (A) Diagram of the cytoplasmic dynein motor complex including the heavy chain (HC) dimer and its associated subunits. A model of the motor domain [5] built from yeast cytoplasmic dynein (PDB ID 4AKG) and the mouse microtubule-binding domain (MTBD) (PDB ID 3ERR) assembled by Dr A.P. Carter has been overlapped with the schematic of the dynein HC in its apo or post-power stroke form [5,93,94]. Adapted, with permission, from The Company of Biologists (J. Cell Sci. 126, 705–713; [4]). The electron micrograph of an isolated molecule of monomeric dynein from Chlamydomonas reinhardtii flagella in its pre-power stroke form is shown for comparison on the right. Adapted with permission from Macmillan Publishers (Nature 421, 715–718; [93]). Conformational changes driven by ATP hydrolysis in the motor domain, which alter the relative position of the stem and the tail/linker, are hypothesised to lead to the power stroke and progression on microtubules [5,94]. The HCs (in dark violet) contain the six AAA ATPase domains (in red), the stalk region, which includes the MTBD (in dark yellow and yellow, respectively), the buttress (in orange), and the linker region. HCs are associated with light intermediate chains (LICs) (in green), intermediate chains (ICs) (in cyan), and light chains (LCs) (in light yellow). (B) Domain composition of the cytoplasmic dynein HC. In addition to the functional domains shown in (A), this scheme displays the homodimerisation region and linker (in white). The positions on the dynein HC of the three mouse mutations (Loa, Legs at odd angles; Cra, Cramping 1; Swl, Sprawling; bottom) and the human mutations discussed in this review (top) are indicated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824068&req=5

fig0005: The cytoplasmic dynein complex. (A) Diagram of the cytoplasmic dynein motor complex including the heavy chain (HC) dimer and its associated subunits. A model of the motor domain [5] built from yeast cytoplasmic dynein (PDB ID 4AKG) and the mouse microtubule-binding domain (MTBD) (PDB ID 3ERR) assembled by Dr A.P. Carter has been overlapped with the schematic of the dynein HC in its apo or post-power stroke form [5,93,94]. Adapted, with permission, from The Company of Biologists (J. Cell Sci. 126, 705–713; [4]). The electron micrograph of an isolated molecule of monomeric dynein from Chlamydomonas reinhardtii flagella in its pre-power stroke form is shown for comparison on the right. Adapted with permission from Macmillan Publishers (Nature 421, 715–718; [93]). Conformational changes driven by ATP hydrolysis in the motor domain, which alter the relative position of the stem and the tail/linker, are hypothesised to lead to the power stroke and progression on microtubules [5,94]. The HCs (in dark violet) contain the six AAA ATPase domains (in red), the stalk region, which includes the MTBD (in dark yellow and yellow, respectively), the buttress (in orange), and the linker region. HCs are associated with light intermediate chains (LICs) (in green), intermediate chains (ICs) (in cyan), and light chains (LCs) (in light yellow). (B) Domain composition of the cytoplasmic dynein HC. In addition to the functional domains shown in (A), this scheme displays the homodimerisation region and linker (in white). The positions on the dynein HC of the three mouse mutations (Loa, Legs at odd angles; Cra, Cramping 1; Swl, Sprawling; bottom) and the human mutations discussed in this review (top) are indicated.
Mentions: Cytoplasmic dynein 1 is a large (∼1.5 MDa), multisubunit motor complex (Figure 1A) that moves towards the minus end of microtubules in eukaryotic cells [1]. It belongs together with the axonemal dyneins and cytoplasmic dynein 2 to the dynein superfamily. Axonemal dyneins are responsible for the movement of cilia and flagella, whereas cytoplasmic dynein 2 has a role in intraflagellar transport and is required for cilia and flagella assembly [1].

Bottom Line: This complex comprises different subunits assembled on a cytoplasmic dynein heavy chain 1 (DYNC1H1) dimer.Cytoplasmic dynein is particularly important for neurons because it carries essential signals and organelles from distal sites to the cell body.Additionally, several DYNC1H1 mutations have recently been found in human patients that give rise to a broad spectrum of developmental and midlife-onset disorders.

View Article: PubMed Central - PubMed

Affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, National Hospital for Neurology and Neurosurgery, University College London, Queen Square, London WC1N 3BG, UK; Molecular NeuroPathobiology, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Electronic address: giampietro.schiavo@ucl.ac.uk.

Show MeSH
Related in: MedlinePlus