Rab27b is Involved in Lysosomal Exocytosis and Proteolipid Protein Trafficking in Oligodendrocytes

Shen, Yuntian; Gu, Yun; Su, Wenfeng; Zhong, Jingfei; Jin, Zi-Han; Gu, Xiaosong; Chen, Gang

doi:10.1007/s12264-016-0045-6

Cited by 30 publications

(21 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some cells use their lysosomes as a regulatory compartment for secretion (Blott & Griffiths, 2002;Holt, Gallo, & Griffiths, 2006;van der Sluijs, Zibouche, & van Kerkhof, 2013;Zhang et al, 2007). Recently, the roles of lysosomal exocytosis in myelin formation were investigated (Chen et al, 2012;Feldmann et al, 2011;Shen et al, 2016;Su et al, 2016). In this study, our data suggested that P2X4R is mainly localized in lysosomes of Schwann cells and P2X4R can be transported to the plasma membrane via lysosomal exocytosis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury

Jin

et al. 2018

Glia

Self Cite

View full text Add to dashboard Cite

Of the seven P2X receptor subtypes, P2X4 receptor (P2X4R) is widely distributed in the central nervous system, including in neurons, astrocytes, and microglia. Accumulating evidence supports roles for P2X4R in the central nervous system, including regulating cell excitability, synaptic transmission, and neuropathic pain. However, little information is available about the distribution and function of P2X4R in the peripheral nervous system. In this study, we find that P2X4R is mainly localized in the lysosomes of Schwann cells in the peripheral nervous system. In cultured Schwann cells, TNF‐a not only enhances the synthesis of P2X4R protein but also promotes P2X4R trafficking to the surface of Schwann cells. TNF‐a‐induced BDNF secretion in Schwann cells is P2X4R dependent. in vivo experiments reveal that expression of P2X4R in Schwann cells of injured nerves is strikingly upregulated following nerve crush injury. Moreover, overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery and accelerates nerve remyelination via BDNF release following nerve injury. Our results suggest that enhancement of P2X4R expression in Schwann cells after nerve injury may be an effective approach to facilitate the regrowth and remyelination of injured nerves.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Immunocytochemistry was performed as previously described (Shen et al, ). Briefly cultured Schwann cells were fixed with 4% paraformaldehyde for 20 min, then blocked with Immunol Staining Blocking Buffer (Beyotime, Haimen, Jiangsu Province, China) for 1 hr at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury

Jin

et al. 2018

Glia

Self Cite

View full text Add to dashboard Cite

show abstract

“…Following the treatment, 2 Â 10 7 cells per treatment were resuspended in 250 mmol/L sucrose/10 mmol/L Tris/HCl buffer solution, which were then disrupted by sonication with two 15-second pulses (Sonics and Materials VCX 600 Watt; ref. 21). The disrupted cells were then subjected to rotation (1,200 Â g for 15 minutes) to remove nuclei and cell debris, and the supernatants were submitted to centrifugation at 30,000 Â g for 30 minutes to achieve the enriched lysosome fraction.…”

Section: Subcellular Fractionationmentioning

confidence: 99%

Itraconazole-Induced Inhibition on Human Esophageal Cancer Cell Growth Requires AMPK Activation

Chen

Liu

Zhou

et al. 2018

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

We here evaluated the antiesophageal cancer cell activity by the antifungal drug itraconazole. Our results show that μg/mL concentrations of itraconazole potently inhibited survival and proliferation of established (TE-1 and Eca-109) and primary human esophageal cancer cells. Itraconazole activated AMPK signaling, which was required for subsequent esophageal cancer cell death. Pharmacologic AMPK inhibition, AMPKα1 shRNA, or dominant negative mutation (T172A) almost completely abolished itraconazole-induced cytotoxicity against esophageal cancer cells. Significantly, itraconazole induced AMPK-dependent autophagic cell death (but not apoptosis) in esophageal cancer cells. Furthermore, AMPK activation by itraconazole induced multiple receptor tyrosine kinases (RTKs: EGFR, PDGFRα, and PDGFRβ), lysosomal translocation, and degradation to inhibit downstream Akt activation. , itraconazole oral gavage potently inhibited Eca-109 tumor growth in SCID mice. It was yet ineffective against AMPKα1 shRNA-expressing Eca-109 tumors. The growth of the primary human esophageal cancer cells was also significantly inhibited by itraconazole administration. AMPK activation, RTK degradation, and Akt inhibition were observed in itraconazole-treated tumors. Together, itraconazole inhibits esophageal cancer cell growth via activating AMPK signaling. .

show abstract

“…An increase in transportation of myelin proteins to the plasma membranes may be essential for E2-induced remyelination, which is dependent on the E2-induced increase in the number of lysosomes. Lysosome of oligodendrocytes and Schwann cells contain abundant myelin proteins, such as PLP and P0, playing an important role in the remyelination of injured nerve via lysosomal exocytosis ( Chen et al, 2012 ; Shen et al, 2016 ; Su et al, 2016 ). We also found that the expression of these two lysosome markers LAMP-1 and myelin protein P0 were significantly increased in E2-treated rats compared with those in vehicle-treated rats after sciatic nerve crush injury.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, accumulating studies have shown that lysosomes in specific cells function in secretory process, which can package bioactive substances and release contents via exocytosis ( Blott and Griffiths, 2002 ; Zhang et al, 2007 ; Ballabio and Gieselmann, 2009 ). A growing number of studies, including our recently study ( Chen et al, 2012 ; Shen et al, 2016 ; Su et al, 2016 ) have shown that the lysosomes of OLs and SCs contain abundant myelin proteins and play an important role in remyelination of injured nerves via the lysosomal exocytosis. In this paper, we would also investigate whether estrogen regulates myelination by enhancing lysosomal exocytosis of Schwann cells.…”

Section: Introductionmentioning

confidence: 96%

17β-Estradiol Enhances Schwann Cell Differentiation via the ERβ-ERK1/2 Signaling Pathway and Promotes Remyelination in Injured Sciatic Nerves

et al. 2018

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Remyelination is critical for nerve regeneration. However, the molecular mechanism involved in remyelination is poorly understood. To explore the roles of 17β-estradiol (E2) for myelination in the peripheral nervous system, we used a co-culture model of rat dorsal root ganglion (DRG) explants and Schwann cells (SCs) and a regeneration model of the crushed sciatic nerves in ovariectomized (OVX) and non-ovariectomized (non-OVX) rats for in vitro and in vivo analysis. E2 promoted myelination by facilitating the differentiation of SCs in vitro, which could be inhibited by the estrogen receptors (ER) antagonist ICI182780, ERβ antagonist PHTPP, or ERK1/2 antagonist PD98059. This suggests that E2 accelerates SC differentiation via the ERβ-ERK1/2 signaling. Furthermore, E2 promotes remyelination in crushed sciatic nerves of both OVX and non-OVX rats. Interestingly, E2 also significantly increased the expression of the lysosome membrane proteins LAMP1 and myelin protein P0 in the regenerating nerves. Moreover, P0 has higher degree of colocalization with LAMP1 in the regenerating nerves. Taking together, our results suggest that E2 enhances Schwann cell differentiation and further myelination via the ERβ-ERK1/2 signaling and that E2 increases the expression of myelin proteins and lysosomes in SCs to promotes remyelination in regenerating sciatic nerves.

show abstract

Rab27b is Involved in Lysosomal Exocytosis and Proteolipid Protein Trafficking in Oligodendrocytes

Cited by 30 publications

References 27 publications

Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury

Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury

Itraconazole-Induced Inhibition on Human Esophageal Cancer Cell Growth Requires AMPK Activation

17β-Estradiol Enhances Schwann Cell Differentiation via the ERβ-ERK1/2 Signaling Pathway and Promotes Remyelination in Injured Sciatic Nerves

Contact Info

Product

Resources

About