The Role Of KIF5B For The Spatiotemporal Regulation Of CDO Pathway During Myoblast Differentiation

The Cdo-p38MAPK signaling pathway plays important roles in regulating skeletal myogenesis. During myogenic differentiation, the cell surface receptor Cdo bridges scaffold proteins BNIP-2 and JLP and activates p38MAPK, but the spatial-temporal regulation of this process is largely unknown. We here report that KIF5B, the heavy chain of Kinesin-1 motor, is a novel interacting partner of BNIP-2. Co-immunoprecipitation study revealed that BNIP-2 interacted with the motor and tail domains of KIF5B via its BCH domain. By using a range of organelle markers and live microscopy, we determined the endosomal localization of BNIP-2 and revealed the microtubule-dependent anterograde transport of BNIP-2 in C2C12 cells. The anterograde transport of BNIP-2 was disrupted by a dominant negative mutant of KIF5B. In addition, knock-down of KIF5B causes aberrant aggregation of BNIP-2, confirming that KIF5B is critical for the anterograde transport BNIP-2 in cells. Gain-and loss-of-function experiments further showed that KIF5B modulates p38MAPK activity and in turn promotes myogenic differentiation. Importantly, the KIF5B-dependent anterograde transport of BNIP-2 is critical for its promyogenic effects. Our data reveal a novel role of KIF5B in the spatial regulation of Cdo-BNIP-2-p38MAPK signaling and disclosed a previously unappreciated linkage between the intracellular transporting system and myogenesis regulation.