KobA mediates kinesin-1-dependent transport of dynein-dynactin to microtubule plus ends
Rongde Qiu, Marisa Delgado, Jun Zhang, Mario Pinar, Paula Polonio, Miguel A Penalva, Xin Xiang
Abstract
Cytoplasmic dynein transports diverse cargoes toward microtubule minus ends following activation by the dynactin complex and cargo adapters. In elongated cells such as fungal hyphae and neurons, dynein must first undergo kinesin-1-dependent transport to microtubule plus ends to engage cargoes, but the mechanism linking these opposing motors remains poorly understood. Here, we identify KobA in the filamentous fungus Aspergillus nidulans as a kinesin-1-binding, coiled-coil protein essential for kinesin-1 (KinA)-mediated plus-end transport of dynein and dynactin. KobA binds the C-terminal cargo-binding domain of KinA. Interestingly, KobA is not required for the general function of KinA in supporting hyphal growth alongside myosin-V, but is specifically required for the microtubule plus-end accumulation of dynein-dynactin even when KinA is activated. Mechanistically, KobA enhances the interaction between KinA and dynactin-dynein. Within its disordered N-terminal region, KobA harbors a Spindly motif typically present in dynein-activating cargo adapters that engage the dynactin pointed end. AlphaFold-3 predictions suggest that the Spindly motif of KobA also binds the dynactin pointed end, and in support of this notion, point mutations within the KobA Spindly motif disrupt the KinA-dynactin association, causing dynein to decorate microtubules rather than accumulate at plus ends. Together, our findings establish KobA as a novel adapter that utilizes a classic cargo adapter Spindly motif to link kinesin-1 to dynein-dynactin, ensuring targeted plus-end delivery of the minus-end motor.
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