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dyneins

Friday 17 October 2003

Dyneins are multisubunit ATPases that participate in several important microtubule-based motilities in eukaryotic cells.

Cytoplasmic dyneins (DNCLs) are microtubule-based biologic motor proteins. Dyneins were initially discovered as enzymes that couple ATP hydrolysis to provide a force for cellular motility in eukaryotic cilia and flagella.

A distinct cytoplasmic form of dynein (MIM.600112) was subsequently characterized and thought to be responsible for the intracellular retrograde motility of vesicles and organelles along microtubules.

At its core, the motor is a ring-shaped object with two protruding levers: one engages cargo and might provide much of the force for movement, and the other interacts with the microtubule track. The activities of both levers are linked through nucleotide-dependent conformational changes in the ring.

Members

- cytoplasmic dynein heavy chains (DNCHs)

DNCH1 DNCH2

- cytoplasmic dynein light chains (DNCLs)

DCNL1

- axonemal dynein heavy chains (DNAHs)

DNAH1 DNAH2 DNAH3 DNAH4 DNAH5 DNAH6 DNAH7 DNAH8 DNAH9 DNAH10
DNAH11 DNAH12 DNAH13 DNAH14 DNAH15 DNAH16 DNAH17 DNAH18

- axonemal dynein intermediate chains (DNAIs)

DNAI1

Function

- At its core, the motor is a ring-shaped object with two protruding levers: one engages cargo and might provide much of the force for movement, and the other interacts with the microtubule track. The activities of both levers are linked through nucleotide-dependent conformational changes in the ring.

- Cytoplasmic dynein is the major minus-end-directed microtubule motor protein in interphase cells. In addition to its well-established roles in vesicular transport and chromosome dynamics, cytoplasmic dynein also associates with the cell cortex.

From this site, it appears to pull on the cytoplasmic microtubule network, influencing mitotic spindle orientation, nuclear position and other aspects of cell polarity and organization.

The cell has the remarkable ability to calculate is geometric center, and, with the help of dynein, to position the centrosome at this central site.

Pathology of dyneins

- Kartagener syndrome (MIM.244400) : mutations in the axonemal dynein intermediate chain (DNAI1)(MIM.604366) (9p21-p13)

- primary ciliary dyskinesia (MIM.242650) (immotile cilia syndrome)

- situs inversus viscerum (MIM.270100) : mutations in axonemal heavy chain dynein 11 (DNAH11) (MIM.603339) (ch. 7)

- Mutations that affect the dynein motor machinery are sufficient to cause motor neuron disease. (15980862)

  • It is not known why there are aggregates or inclusions in affected tissues in mice with such mutations and in most forms of human motor neuron disease.
  • Decreased dynein function impairs autophagic clearance of aggregate-prone proteins.
  • Mutations of the dynein machinery enhanced the toxicity of the mutation that causes Huntington disease in fly and mouse models.
  • Loss of dynein function resulted in premature aggregate formation by mutant huntingtin and increased levels of the autophagosome marker LC3-II, compatible with impaired autophagosome-lysosome fusion.

See also:

- motor proteins

Animations

- Axonal transport: A movie from J Cell Biol

References

- Ravikumar B, Acevedo-Arozena A, Imarisio S, Berger Z, Vacher C, O’Kane CJ, Brown SD, Rubinsztein DC. Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nat Genet. 2005 Jul;37(7):771-6. PMID: 15980862

- Vallee RB, Stehman SA. How dynein helps the cell find its center: a servomechanical model. Trends Cell Biol. 2005 Jun;15(6):288-94. PMID: 15953546

- Koonce MP, Samso M. Of rings and levers: the dynein motor comes of age. Trends Cell Biol. 2004 Nov;14(11):612-9. PMID: 15519850

- Karcher RL, Deacon SW, Gelfand VI. Motor-cargo interactions : the key to transport specificity. Trends Cell Biol. 2002 Jan ;12(1):21-7. PMID : 11854006

- Goldstein LS. Molecular motors: from one motor many tails to one motor many tales. Trends Cell Biol. 2001 Dec;11(12):477-82. PMID: 11719052

- Asai DJ, Koonce MP. The dynein heavy chain: structure, mechanics and evolution. Trends Cell Biol. 2001 May;11(5):196-202. PMID: 11316608