An investigation into the interphase neuronal function of the kinesin 12 motor Kif15

Effective intracellular transport and meticulous microtubule organisation are the cornerstones of successful neuronal function. The kinesin-12, Kif15 is most commonly known for its role in mitosis where it slides the mitotic spindle however, depletion studies have revealed a role for Kif15 in accurate neuronal formation and neuronal guidance; Kif15 depletion increases axonal length and decreases branching, as well as enhancing neuronal migration speed and having smaller growth cones. Kif15 is able to both organise microtubules as a tetramer and effectively transport cargo, as well as being able to directly bind to actin. Here, I demonstrate that Kif15 is important for the migration speed and directionality of RPE cells with knockout which can then be rescued by re-expression, and the organisation of microtubules during interphase in RPE cells. Additionally, I have shown in our neuronal system of LUHMES cells, Kif15 affects NPY cargo and increases the bundling of neurites during neuronal outgrowth. Kif15 inhibition shows a trend of increasing the number of transport events of tagged NPY cargo in differentiated neurons, however the same cannot be said for Rab7a. Here I demonstrate that Kif15 inhibition leads to more fragmented transport of NPY cargo by increasing the number of pauses and reversals of NPY cargo and assessed whether this effect could be related to acetylation of microtubules. I have also reported global changes in differentiated neurons, namely that growth cones of Kif15 depleted neurons are smaller.