Moonlighting Motors: Kinesin, Dynein, and Cell Polarity

In addition to their well-known role in transporting cargoes in the cytoplasm, microtubule motors organize their own tracks – the microtubules. While this function is mostly studied in the context of cell division, it is essential for microtubule organization and generation of cell polarity in interphase cells. Kinesin-1, the most abundant microtubule motor, plays a role in the initial formation of neurites. This review describes the mechanism of kinesin-1-driven microtubule sliding and discusses its biological significance in neurons. Recent studies describing the interplay between kinesin-1 and cytoplasmic dynein in the translocation of microtubules are discussed. In addition, we evaluate recent work exploring the developmental regulation of microtubule sliding during axonal outgrowth and regeneration. Collectively, the discussed works suggest that sliding of interphase microtubules by motors is a novel force-generating mechanism that reorganizes the cytoskeleton and drives shape change and polarization. Contrary to the textbook view, cytoplasmic microtubules in interphase cells are not static; they robustly slide in the cytoplasm moved by microtubule motors. Two motors contribute to microtubule sliding: kinesin-1 that slides microtubules against each other, and cytoplasmic dynein that drives microtubule movement relative to the cell cortex. Sliding microtubules can drive cell shape change by pushing against the plasma membrane. Plus-end motor kinesin-1 and minus-end motor dynein cooperate to achieve the correct microtubule organization in the axons. Microtubule sliding activity is developmentally regulated independently of the global regulation of the motor activity. F-actin in the growth cone of growing neurites antagonizes the neurite outgrowth by preventing sliding microtubules from penetrating into the growth cone. Cargoes can be transported by hitchhiking on moving microtubules.