VezA/vezatin facilitates proper assembly of the dynactin complex in vivo

Abstract

Cytoplasmic dynein-mediated intracellular transport needs the multi-component dynactin complex for cargo binding and motor activation. However, cellular factors involved in dynactin assembly remain unexplored. Here we found in Aspergillus nidulans that the vezatin homolog VezA is important for dynactin assembly. VezA affects the microtubule plus-end accumulation of dynein before cargo binding and cargo adapter-mediated dynein activation, two processes that both need dynactin. The dynactin complex contains multiple components including an Arp1 (actin-related protein 1) mini-filament associated with a pointed-end sub-complex. VezA physically interacts with dynactin either directly or indirectly via the Arp1 mini-filament and its pointed-end sub-complex. Loss of VezA causes a defect in dynactin integrity, most likely by affecting the connection between the Arp1 mini-filament and its pointed-end sub-complex. Using various dynactin mutants, we further revealed that assembly of the dynactin complex must be highly coordinated. Together, these results shed important new light on dynactin assembly in vivo.