Dynactin

Dynactin is a multi-subunit cytoplasmic protein complex that serves as a key cofactor for cytoplasmic dynein, linking dynein to cargo and to microtubules to drive minus-end–directed transport along the microtubule network. It is essential for efficient retrograde transport in many cell types, including neurons, where it supports movement of organelles, vesicles, and proteins toward the cell center.

The complex is built around an actin-related protein 1 (Arp1)–based core filament with a projecting sidearm. A prominent subunit, p150Glued, sits at the tip of this arm and participates in dynein binding and microtubule interactions. Dynactin also includes several other subunits, such as dynamitin (p50), p24, p27, p22, and p18 in humans, among others, which stabilize the complex and regulate its interaction with dynein and cargo adaptors.

Functionally, dynactin acts as a bridge that connects dynein to a wide range of cargo, enabling processive movement toward microtubule minus ends. It also participates in mitotic spindle function, organelle positioning, and other dynein-dependent processes. The p150Glued subunit contains a CAP-Gly domain that binds microtubules and plus-end tracking factors, enhancing dynein processivity and cargo attachment. Dynactin activity is modulated by interactions with dynein regulators and cargo adaptors.

Clinical relevance includes mutations in DCTN1, which encodes p150Glued, associated with Perry syndrome and other neurodegenerative conditions, underscoring the importance of dynactin in neuronal transport and health. Dynactin is evolutionarily conserved across eukaryotes and remains central to dynein-mediated motility.