KIF5B transports BNIP-2 to regulate p38 mitogen-activated protein kinase activation and myoblast differentiation
| Autor: | Feiya Wang, Hao Ren, Li Li Chew, Boon Chuan Low, Peng Yi, Hongwei Ouyang, Yi Ting Zhou, Xiaoxia Cong, Ziwang Zhang, Yan Luo, Liling Zheng |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Scaffold protein
MAP Kinase Signaling System Endosome Cellular differentiation Molecular Sequence Data Kinesins Endosomes Biology Muscle Development Microtubules p38 Mitogen-Activated Protein Kinases Cell Line Myoblasts Humans Myocyte Amino Acid Sequence Cell Interactions Protein kinase A Molecular Biology Myogenesis Biological Transport Cell Differentiation Articles Cell Biology Cell biology Signal transduction Carrier Proteins C2C12 Protein Binding |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Cdo bridges scaffold proteins BNIP-2 and JLP to activate p38MAPK during myoblast differentiation. KIF5B is a novel interacting partner of BNIP-2 and promotes myogenic differentiation. KIF5B-dependent transport of BNIP-2 is essential for its promyogenic effects. The Cdo-p38MAPK (p38 mitogen-activated protein kinase) 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. Coimmunoprecipitation and far-Western study revealed that BNIP-2 directly 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, knockdown of KIF5B causes aberrant aggregation of BNIP-2, confirming that KIF5B is critical for the anterograde transport of BNIP-2 in cells. Gain- and loss-of-function experiments further showed that KIF5B modulates p38MAPK activity and in turn promotes myogenic differentiation. Of importance, 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 disclose a previously unappreciated linkage between the intracellular transporting system and myogenesis regulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|