UC Irvine

Kinesin-1 is a plus-end microtubule-based motor, and defects in kinesin-basedtransport are linked to diseases including neurodegeneration. Kinesin canauto-inhibit via a direct head-tail interaction, but is believed to be active otherwise.Here we report a tail-independent inactivation of kinesin, reversibleby the disease-relevant signaling protein, casein kinase 2 (CK2). The majorityof initially active kinesin (native or tail-less) loses its ability to bind/interactwith microtubules in vitro, and CK2 reverses this inactivation (~ 4-fold)without altering kinesin’s single motor properties. This activation pathwaydoes not require motor phosphorylation, and is independent of head-tail autoinhibition.In cultured mammalian cells, reducing CK2 expression, but notkinase activity, decreases the force required to stall lipid droplet transport, consistentwith a reduction in the number of active motors. These results providethe first direct evidence of a protein kinase up-regulating kinesin-based transport,and suggest a novel pathway for regulating the activity of cargo-boundkinesin.