In intracellular transport Dynactin p27 forms a hetero-dimer with the other dynactin pointed-end complex subunit p25/DCTN5 in 1:1 ratio, and it is essential for p25 stability since they are co-knockdown by p27 RNAi. However, both p27 and p25 are not required for 19S dynactin complex integrity verified by velocity sedimentation. p27/DCTN6 and other dynactin pointed-end complex subunits (Arp11/
Actr10, p62/
DCTN4, and p25/
DCTN5) have been suggested to be involved in dynactin binding to specific intracellular cargoes. Co-depletion of dynactin p27 and p25 by p27 RNAi affects dynactin binding to endomembrane, and early and recycling
endosome movements are impaired, suggesting that p27/p25 form a selective endomembrane cargo-targeting module.
In mitosis In
mitosis, unlike dynactin or dynein perturbation that causes
mitotic spindle disarrangement and mitotic arrest, dynactin p27/p25 depletion does not affect mitotic spindle formation, pole focusing or dynein/dynactin targeting to
kinetochores. However, dynactin p27/p25 are required for normal
chromosome alignment, kinetochore-microtubule interaction, and proper timing of anaphase onset. Dynactin p27 C-terminal T186 residue is phosphorylated by
cyclin-dependent kinase 1 (
Cdk1) in mitosis and helps target
polo-like kinase 1 (
Plk1) to kinetochores during
prometaphase. This activity facilitates phosphorylation of important downstream kinetochore targets (such as tension-sensing 3F3/2 phospho-epitope) of
Plk1, which is important for recruitment of spindle assembly checkpoint proteins such as
Mad1 and proper kinetochore-microtubule attachment. == References ==