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Yi P.,Center for Stem Cell and Tissue Engineering | Yi P.,Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine | Chew L.L.,National University of Singapore | Zhang Z.,Center for Stem Cell and Tissue Engineering | And 12 more authors.
Molecular Biology of the Cell | Year: 2015

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. Coimmu-noprecipitation 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 microtu-bule-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 antero-grade 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. © 2015 Yi, Chew, Zhang, et al.


Wang L.-L.,Center for Stem Cell and Tissue Engineering | Shi D.-L.,Center for Stem Cell and Tissue Engineering | Gu H.-Y.,Zhejiang University | Zheng M.-Z.,Zhejiang Medical College | And 4 more authors.
Molecular Medicine Reports | Year: 2016

The present study aimed to investigate the effect of resveratrol on inflammatory pain. Mice were injected intraperitoneally with lipopolysaccharide (LPS) for 5 consecutive days to induce subacute systemic inflammation. Acetic acid-induced writhing tests and tail-flick tests were performed following the final LPS injection. Glial fibrillary acidic protein (GFAP; an astrocyte-specific activation marker), ionized calcium binding adapter molecule 1 (Iba-1; a microglia-specific activation marker) and sirtuin 1 (SIRT1) protein expression levels were detected using immunohistochemistry analysis or western blotting. Following administration of LPS for 5 days, the number of writhes increased and the tail-flick latency decreased. Resveratrol (10 or 20 mg/kg) partly inhibited LPS-induced hyperalgesia and prevented the increase in tumor necrosis factor-α and interleukin 6 levels induced by LPS. LPS injection reduced the SIRT1 protein expression and increased the number of GFAP-positive and Iba-1-positive cells in the spinal cord. Resveratrol increased the SIRT1 protein expression levels and decreased the number of GFAP-positive and Iba-1-positive cells in LPS-treated mice. The protective effect of resveratrol was partly blocked by a selective SIRT1 inhibitor, EX-257. Results from the present study suggest that subacute treatment with LPS induced the activation of glial cells and hyperalgesia. Resveratrol was demonstrated to inhibit the activation of glial cells and attenuate inflammatory hyperalgesia in a SIRT1-dependent manner.


PubMed | Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, National University of Singapore and Center for Stem Cell and Tissue Engineering
Type: Journal Article | Journal: Molecular biology of the cell | Year: 2014

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.

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