KIF5B transports BNIP-2 to regulate p38 mitogen-activated protein kinase activation and myoblast differentiation

Peng, Yi; Chew, Li Li; Zhang, Ziwang; Ren, Hao; Wang, Feiya; Cong, Xiaoxia; Zheng, Liling; Luo, Yan; Ouyang, Hongwei; Low, Boon Chuan; Zhou, Yi

doi:10.1091/mbc.e14-03-0797

Cited by 17 publications

(26 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cells were seeded on coverslips in six‐well plates and stained for immunofluorescence detection using confocal fluorescence microscopy as previously described . Filamentous actin was detected by rhodamine‐phalloidin (Molecular Probes) and Collagen I was detected by anti‐Collagen I (abcam, Cambridge, MA) followed by Alexa Fluor 488‐conjugated goat anti‐mouse IgG (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Activation of AKT-mTOR Signaling Directs Tenogenesis of Mesenchymal Stem Cells

Cong

Rao

Lin³

et al. 2018

Stem Cells

Self Cite

View full text Add to dashboard Cite

Tendon repair is a clinical challenge because of the limited understanding on tenogenesis. The synthesis of type I collagen (Collagen I) and other extracellular matrix are essential for tendon differentiation and homeostasis. Current studies on tenogenesis focused mostly on the tenogenic transcriptional factors while the signaling controlling tenogenesis on translational level remains largely unknown. Here, we showed that mechanistic target of rapamycin (mTOR) signaling was activated by protenogenic growth factor, transforming growth factors beta1, and insulin-like growth factor-I. The expression of mTOR was upregulated during tenogenesis of mesenchymal stem cells (MSCs). Moreover, mTOR was downregulated in human tendinopathy tissues and was inactivated upon statin treatment. Both inhibition and depletion of AKT or mTOR significantly reduced type I collagen production and impaired tenogenesis of MSCs. Tendon specific-ablation of mTOR resulted in tendon defect and reduction of Collagen I. However, there is no evident downregulation of tendon associated collagens at the transcription level. Our study demonstrated that AKT-mTOR axis is a key mediator of tendon differentiation and provided a novel therapeutic target for tendinopathy and tendon injuries. Stem Cells 2018;36:527-539.

show abstract

Section: Methodsmentioning

confidence: 99%

Activation of AKT-mTOR Signaling Directs Tenogenesis of Mesenchymal Stem Cells

Cong

Rao

Lin³

et al. 2018

Stem Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…The secreted ACh promotes neuritogensis by activating ERK through muscarinic receptors and elicits postsynaptic neurotransmission. et al, 2015) and kinesin heavy chain (Yi et al, 2015). During muscle development, BNIP-2 functions as a scaffold that links Cdo receptor for the activation of Cdc42.…”

Section: Functional Specificity Of Bch Domain Family Proteinsmentioning

confidence: 99%

“…Together with another scaffold, JLP, it leads to p38 activation at cell membrane (Kang et al, 2008). Kinesin-1 is proposed to regulate this process by anterogradely transporting BNIP-2 to cell membrane to allow it to interact with Cdo receptor for p38 activation (Yi et al, 2015). Unlike the properties of BNIP-H, BNIP-2 fails to recognize ACL and does not regulate cholinergic signaling for neurite outgrowth.…”

Section: Functional Specificity Of Bch Domain Family Proteinsmentioning

confidence: 99%

BNIP-H Recruits the Cholinergic Machinery to Neurite Terminals to Promote Acetylcholine Signaling and Neuritogenesis

et al. 2015

View full text Add to dashboard Cite

Synthesis and release of neurotransmitters such as acetylcholine (ACh) are key to synaptic function. However, little is known about the spatial regulation of their synthesizing machinery. Here, we demonstrate that ataxia-related protein BNIP-H/Caytaxin links kinesin-1 (KLC1) to ATP citrate lyase (ACL), a key enzyme for ACh synthesis, and transports it toward neurite terminals. There, BNIP-H/ACL complex synergistically recruits another enzyme choline acetyltransferase (ChAT), leading to enhanced secretion of ACh. ACh then activates MAPK/ERK via muscarinic receptors to promote neurite outgrowth. In mice deficient in BNIP-H, ACL fails to interact with KLC1, and formation of the ACL/ChAT complex is prevented, whereas the disease-associated BNIP-H mutation fails to target ACL for neurite outgrowth. Significantly, Bnip-h knockdown in zebrafish causes developmental defect in motor neurons through impaired cholinergic pathway, leading to motor disorder. Therefore, precise targeting of the cholinergic machinery through BNIP-H is essential for the local production of ACh for morphogenesis and neurotransmission.

show abstract

“…Besides phosphorylation, additional regulatory mechanisms were found to control p38MAPK signaling. Our previous findings revealed that the spatial regulation of this signaling complex is dependent on KIF5B-dependent anterograde transport (19). In addition, the stability of p38MAPK is regulated by association with MAPK-activated protein kinase 2 (MK2) or MAPK-activated protein kinase 3 (MK3).…”

mentioning

confidence: 99%

Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration

Fan

Gao

Rao

et al. 2018

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblasts derived from muscle stem cells. Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration, but the precise cellular mechanism remains elusive. In this study, we found that Hsp70 was upregulated during myoblast differentiation. Depletion or inhibition of Hsp70/Hsc70 impaired myoblast differentiation. Importantly, overexpression of p38 mitogen-activated protein kinase α (p38MAPKα) but not AKT1 rescued the impairment of myogenic differentiation in Hsp70- or Hsc70-depleted myoblasts. Moreover, Hsp70 interacted with MK2, a substrate of p38MAPK, to regulate the stability of p38MAPK. Knockdown of Hsp70 also led to downregulation of both MK2 and p38MAPK in intact muscles and during cardiotoxin-induced muscle regeneration. Hsp70 bound MK2 to regulate MK2-p38MAPK interaction in myoblasts. We subsequently identified the essential regions required for Hsp70-MK2 interaction. Functional analyses showed that MK2 is essential for both myoblast differentiation and skeletal muscle regeneration. Taken together, our findings reveal a novel role of Hsp70 in regulating myoblast differentiation by interacting with MK2 to stabilize p38MAPK.

show abstract

KIF5B transports BNIP-2 to regulate p38 mitogen-activated protein kinase activation and myoblast differentiation

Abstract: 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.

Cited by 17 publications

References 62 publications

Activation of AKT-mTOR Signaling Directs Tenogenesis of Mesenchymal Stem Cells

Activation of AKT-mTOR Signaling Directs Tenogenesis of Mesenchymal Stem Cells

BNIP-H Recruits the Cholinergic Machinery to Neurite Terminals to Promote Acetylcholine Signaling and Neuritogenesis

Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration

Contact Info

Product

Resources

About