dyneins

Dyneins are a family of large ATP-dependent motor proteins that move along microtubules toward the minus end. They convert chemical energy from ATP hydrolysis into mechanical work, powering many cellular movements, including retrograde transport toward the cell center and the beating of cilia and flagella.

Two broad classes are recognized: cytoplasmic dyneins, which drive intracellular transport and chromosome movement during cell division, and axonemal dyneins, which power the bending of cilia and flagella. Cytoplasmic dynein 1 (dynein-1) handles most organelle and vesicle transport, while cytoplasmic dynein 2 (dynein-2) participates in intraflagellar transport in cilia.

Dyneins are large multi-subunit complexes. The core motor is the dynein heavy chain, containing a AAA+ ATPase ring and a microtubule-binding stalk. The complex also includes intermediate and light chains that assemble with cargo adaptors to regulate binding and specificity.

Movement is driven by ATP binding and hydrolysis cycles in the AAA+ ring, producing conformational changes that generate sliding or stepping along the microtubule. Processivity and cargo attachment are enhanced by cofactors such as dynactin and various adaptor proteins; Lis1 regulates dynein function during development and transport.

Dynein serves essential cellular roles, including retrograde transport of organelles, vesicles, and RNAs; positioning of nuclei and spindles during mitosis; and, in neurons, retrograde signaling along axons. Axonemal dyneins in cilia and flagella generate the sliding of microtubule doublets that produces beating.

Defects in dynein components or regulators cause human disease, referred to as dyneinopathies. These include neurodevelopmental disorders and ciliopathies; disruptions of dynactin or Lis1 can contribute to impaired transport and brain malformations such as lissencephaly.