[Research Progress in the Roles of MRE11-RAD50-NBS1 Complex and Human Diseases].

DNA is susceptible to various factors in vitro and in vivo and experience different forms of damage,among which double-strand break(DSB)is a deleterious form.To maintain the stability of genetic information,organisms have developed multiple mechanisms to repair DNA damage.Among these mechanisms,homologous recombination(HR)is praised for the high accuracy.The MRE11-RAD50-NBS1(MRN)complex plays an important role in HR and is conserved across different species.The knowledge on the MRN complex mainly came from the previous studies in Saccharomyces cerevisiae and Caenorhabditis elegans,while studies in the last decades have revealed the role of mammalian MRN complex in DNA repair of higher animals.In this review,we first introduces the MRN complex regarding the composition,structure,and roles in HR.In addition,we discuss the human diseases such as ataxia-telangiectasia-like disorder,Nijmegen breakage syndrome,and Nijmegen breakage syndrome-like disorder that are caused by dysfunctions in the MRN complex.Furthermore,we summarize the mouse models established to study the clinical phenotypes of the above diseases.

Influence of PD-1/PD-L1 on immune microenvironment in oral leukoplakia and oral squamous cell carcinoma.

OBJECTIVE: To evaluate the relation between the expression of PD-1, PD-L1, CD3, CD8, Foxp3 and clinicopathological features in patients with oral leukoplakia (OLK) and oral squamous cell carcinomas (OSCC) as well as the malignant outcome in OLK patients, and to study the effect of PD-1 and PD-L1 on immune microenvironment in the progression of oral carcinogenesis. METHODS: We evaluated the expression of PD-1/PD-L1 and composition of CD3+ , CD8+ and Foxp3+ T lymphocytes in OLK and OSCC samples by immunohistochemical (IHC) staining and analyzed their relation with clinical information and malignant transformation in OLK patients. RESULTS: IHC staining demonstrated that the expression of PD-1 was significantly increased in the high-grade OLK group than in the low-grade OLK group, while PD-L1 was detected mainly in OSCC. The expression of CD3, CD8, and Foxp3 was found higher in the high-grade OLK group than in the low-grade OLK group, and the Foxp3+ cells were found more in the OSCC group than in the high-grade OLK group. PD-1 was significantly correlated with CD3 (p < 0.05, R = 0.52), CD8 (p < 0.05, R = 0.46), and Foxp3 (p < 0.05, R = 0.46), and the low PD-1-expression group showed a better malignant-free survival than high PD-1 expression group in the OLK (p < 0.05). CONCLUSION: The PD-1/PD-L1 may induce immune suppression in OLK and accelerate the progress of malignant transformation.

Tex264 Binding to SNX27 Regulates Itgα5 Receptor Membrane Recycling and Affects Cell Migration.

Tex264 is an endoplasmic reticulum (ER) membrane protein that was recently demonstrated to act as an ER-phagy receptor under starvation conditions to mediate endoplasmic reticulum autophagy. However, how Tex264 functions in the central nervous system (CNS) and tumors is unclear. Here, we identified 89 proteins from the rat brain that may specifically interact with Tex264 and confirmed the interaction between sorting nexin 27 (SNX27) and Tex264 by coimmunoprecipitation and immunofluorescence. Our results indicated that Tex264 may promote recycling of membrane proteins from endosomes to the cell plasma membrane by recruiting SNX27 retromer vesicles. siRNA-mediated knockdown of TEX264 in HeLa cells did not affect cell proliferation but did significantly inhibit cell migration through a mechanism that may involve a reduction in SNX27-mediated Itgα5 receptor membrane recycling. Results of this study helped identify potential binding Tex264 partners and provide insights into Tex264 functions in the CNS and in tumors.

Long noncoding RNA X-inactive specific transcript regulates NLR family pyrin domain containing 3/caspase-1-mediated pyroptosis in diabetic nephropathy.

BACKGROUND: NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology. Long noncoding RNAs (lncRNAs) are active participators of diabetic nephropathy (DN). X inactive specific transcript (XIST) expression has been reported to be elevated in the serum of DN patients. AIM: To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell (RTEC) pyroptosis in DN. METHODS: A DN rat model was established through streptozotocin injection, and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST. Renal metabolic and biochemical indices were detected, and pathological changes in the renal tissue were assessed. The expression of indicators related to inflammation and pyroptosis was also detected. High glucose (HG) was used to treat HK2 cells, and cell viability and lactate dehydrogenase (LDH) activity were detected after silencing XIST. The subcellular localization and downstream mechanism of XIST were investigated. Finally, a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3 (NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p (miR-15b-5p)/Toll-like receptor 4 (TLR4) axis. RESULTS: XIST was highly expressed in the DN models. XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury. The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells; cell viability was decreased and LDH activity was increased after HG treatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically, XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promoting miR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect of silencing XIST on HG-induced RTEC pyroptosis. CONCLUSION: Silencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury in DN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.

WNK3-PER1 interactions regulate the circadian rhythm in the suprachiasmatic nucleus in rats.

PER1 is a core component of the internal time-keeping system. In the suprachiasmatic nucleus, it serves as the primary circadian pacemaker in mammalian brains. PER1 functions with other clock components to generate a feedback loop involving the transcriptional repression of gene expression to produce a circadian rhythm with an approximately 24-hour cycle. Post-transcriptional modifications (PTMs) are a basic regulatory mechanism that both perpetuate self-sustained oscillations and interpret metabolic input into circadian physiology by affecting factors such as protein stability, interactions, localization, and activity. Here we examined whether the serine/threonine protein kinase WNK3, which is expressed in a circadian rhythm, can interact and colocalize with PER1 in the SCN. In rats, WNK3 knockdown in the SCN is associated with altered sleep patterns. Moreover, WNK3 can phosphorylate PER1 to promote its degradation and is associated with circadian oscillations when PER1 is expressed in vitro.

Transient expression of thyrotropin releasing hormone peptide and mRNA in the rat hippocampus following global cerebral ischemia/reperfusion injury.

INTRODUCTION: The role of extra-hypothalamic thyrotropin-releasing hormone (TRH) has been investigated by pharmacological studies using TRH or its analogues and found to produce a wide array of effects in the central nervous system. METHODS: Immunofluorescence, In situ labeling of DNA (TUNEL), in situ hybridization chain reaction and quantitative real-time polymerase chain reaction were used in this study. RESULTS: We found that the granular cells of the dentate gyrus expressed transiently a significant amount of TRH-like immunoreactivity and TRH mRNA during the 6-24 h period following global cerebral ischemia/reperfusion injury. TUNEL showed that apoptosis of neurons in the CA1 region occurred from 48 h and almost disappeared at 7 days. TRH administration 30 min before or 24 h after the injury could partially inhibit neuronal loss, and improve the survival of neurons in the CA1 region. CONCLUSION: These data suggest that endogenous TRH expressed transiently in the dentate gyrus of the hippocampus may play an important role in the survival of neurons during the early stage of ischemia/reperfusion injury and that delayed application of TRH still produced neuroprotection. This delayed application of TRH has a promising therapeutic significance for clinical situations.

Medium-Term Clinical Results of High-Flexion Knee Prostheses in Patients with Rheumatoid Arthritis.

OBJECTIVE: This study was performed to evaluate the function and satisfaction outcome of patients with rheumatoid arthritis (RA) who underwent total knee arthroplasty (TKA) with high-flexion prostheses. MATERIALS AND METHODS: Twenty-two patients (35 knees) using high-flexion prostheses (Zimmer, Warsaw, IN) were followed up for a period of 7-11 years from February 2007 to December 2009. Clinical and radiographic follow-up was performed using Hospital for Special Surgery (HSS), Short-Form 36 scores (SF-36), American Knee Society score (KSS), and Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. Patient satisfaction assessments took place at the final follow-up sessions using the Marsh Satisfaction Questionnaire. RESULTS: The average ROM improved from preoperative 68.43° ± 33.78° to 95.54° ± 7.03° at the final follow-up. The HSS score and KSS score for pain improved from (46.49 ± 12.73) points to (85.46 ± 3.90) points and from 20.57 ± 5.91 points to 47.43 ± 3.51 points at the follow-up evaluation, respectively. Physical Component Summary(PCS) and Physical Component Summary (MCS) scores were 45.38 and 52.56, respectively by the end of follow-up. Deep venous thrombosis developed in one patient and one patient required surgical revision due to infection. There were no instances of prosthetic loosening. The satisfaction rate of patients was 95.5%. CONCLUSION: Although this particular model of TKA did not yield high-flexion angles (ie, 140°) required for kneeling, squatting, or rising from the floor, significant clinical and radiographic gains were evident in these patients with RA.

The magnetic-nanoparticle-assisted sensitive detection of nitrated α-syn in blood based on a sensitizing electrochemical layer.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. Nitrated α-synuclein (α-syn) in the blood is a potentially efficient biomarker for PD in its early stages. In this work, an ultrasensitive electrochemical immunosensor was developed for the specific detection of nitrated α-syn. Supramolecule-mediated AuNP composites (GNCs) were modified on the gold electrode as a sensing film to capture anti-nitrated α-syn. Basic characterization studies revealed that GNCs were composed of abundant binding sites and had high conductivity with a large surface area, biocompatibility, and remarkable electrochemical activity. Anti-α-syn-modified magnetic nanoparticles (MNPs) were used as signal amplification tags to construct a sensitive sandwich assay. With a high specific surface area, strong conductivity, and abundant active sites, GNCs as an amplifying matrix can enhance the performance of the immunoassay and obtain preliminary signal amplification. MNPs showed excellent stability and led to a net decrease in the charge-transfer resistance due to their unique spherical structure and high conductivity, resulting in a sensitive electrochemical signal change according to the nitrated α-syn concentration in the sample. Therefore, this simple nitrated α-syn immunoassay with sensitivity and selectivity has potential for practical clinical applications.

Revealing PAK2's Function in the Cell Division through MKLP1's Interactome.

Cell division-related proteins are essential for the normal development and differentiation of cells and may be related to the occurrence of cancer and the drug resistance mechanism of cancer cells. The mitotic kinesin-like protein 1 (MKLP1) is a kinesin protein that has been involved in the assembly of the midzone/midbody during mitosis and cytokinesis. In this study, we found that the tail domain of MKLP1 exhibited an autoinhibitory effect on its motor activity. Overexpression of the tail domain in HEK293 cells blocked cytokinesis and caused bi-/multinucleation. It is possible that protein binding to the MKLP1 tail relieves this autoinhibition and induces the motility of MKLP1. We used the GST pull-down assay followed by the LC-MS/MS analysis and identified 54 MKLP1 tail domain-specific binding proteins. Further, we confirmed the MS result by coimmunoprecipitation and FRET that a serine/threonine kinase, p21-activated kinase 2 (PAK2), binding to MKLP1. Endogenous PAK2 expression was found to be identical to that of MKLP1 in HEK293 cells during cytokinesis. Finally, functional studies indicated that when PAK2 expression was downregulated by siRNA, MKLP1 underwent a change in its localization away from the midbody, and cell cytokinesis was subsequently impeded. This study presents a novel regulatory mechanism that PAK2 promotes the activation of MKLP1 and contributes to complete cell cytokinesis.

Circ-camk4 involved in cerebral ischemia/reperfusion induced neuronal injury.

Stroke and subsequent cerebral ischemia/reperfusion (I/R) injury is a frequently occurring disease that can have serious consequences in the absence of timely intervention. Circular RNAs (circRNAs) in association with microRNAs (miRNAs) and RNA-binding proteins (RBPs) can influence gene expression. However, whether circRNAs have a role in cerebral I/R injury pathogenesis, especially soon after onset, is unclear. In this study, we used the SD rat middle cerebral artery occlusion (MCAO) model of stroke to examine the role of circRNAs in cerebral I/R injury. We used high-throughput sequencing (HTS) to compare the expression levels of circRNAs in cerebral cortex tissue from MCAO rats during the occlusion-reperfusion latency period 3 hours after I/R injury with those in control cerebral cortices. Our sequencing results revealed that expression levels of 44 circRNAs were significantly altered after I/R, with 16 and 28 circRNAs showing significant up- and down-regulation, respectively, relative to levels in control cortex. We extended these results in vitro in primary cultured neuron cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R) using qRT-PCR to show that levels of circ-camk4 were increased in OGD/R neurons relative to control neurons. Bioinformatics analyses predicted that several miRNAs could be associated with circ-camk4 and this prediction was confirmed in a RNA pull-down assay. KEGG analysis to predict pathways that involve circ-camk4 included the glutamatergic synapse pathway, MAPK signaling pathway, and apoptosis signaling pathways, all of which are known to be involved in brain injury after I/R. Our results also demonstrate that levels of the human homolog to circ-camk4 (hsa-circ-camk4) are elevated in SH-SY5Y cells exposed to OGD/R treatment. Overexpression of hsa-circ-camk4 in SH-SY5Y cells significantly increased the rate of cell death after OGD/R, suggesting that circ-camk4 may play a key role in progression of cerebral I/R injury.

Increasing the methane production rate of hydrogenotrophic methanogens using biochar as a biocarrier.

The existence of CO2 in biogas will affect its practicality, so the methanation of CO2 is of great significance. Carrier materials play a key role in bioconversion of CO2 to methane during biogas upgrading. Herein, different materials were used to evaluate the bioconversion process of CO2 to methane, which consisted of black ceramsite (BC) and biochars prepared from corn straw and digestate. The results showed that after adding the carrier materials, the methane production rate increased by more than 20%, and the corn straw biochar (CSB) group even increased by more than 70%. This may be attributed to the large specific surface area and more functional groups in corn straw biochar which was suitable for the immobilization of hydrogenotrophic methanogens (HMs). Therefore, corn straw biochar is a good carrier material for the accelerated bioconversion of CO2 to methane.

OsmiR530 acts downstream of OsPIL15 to regulate grain yield in rice.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that play important roles in plant growth and development as well as in stress responses. However, little is known about their regulatory functions affecting rice grain yield. We functionally characterized a novel miRNA in rice, OsmiR530, its target OsPL3, and its upstream regulator phytochrome-interacting factor-like 15 (OsPIL15). Their effects on rice yield were dissected comprehensively. We determined that OsmiR530 negatively regulates grain yield. Blocking OsmiR530 increases grain yield, whereas OsmiR530 overexpression significantly decreases grain size and panicle branching, leading to yield loss. Additionally, OsPL3, which encodes a PLUS3 domain-containing protein, is targeted directly by OsmiR530. Knocking out OsPL3 decreases the grain yield. In-depth analyses indicated that OsPIL15 activates OsMIR530 expression by directly binding to the G-box elements in the promoter. Analyses of genetic variations suggested that the OsMIR530 locus has likely been subjected to artificial selection during rice breeding. The results presented herein reveal a novel OsPIL15-OsmiR530 module controlling rice grain yield, thus providing researchers with a new target for the breeding of high-yielding rice.

SIRT 1 binding with PKM and NSE and modulate their acetylation and activities.

SIRT1 (Silent mating type information regulation 2 homolog 1) play a neuroprotective effect through deacetylation target proteins in various neuronal diseases. However, the precise mechanisms remain elusive. In this study, we aim to identify those novel interacting partners of SIRT1 in rat brain tissue. By using a pre-clear GST-Pull down assay followed by the LC-MS/MS analysis, we've identified potential SIRT1's interacting partners, which function annotation by GO and KEGG analysis indicating some metabolic pathways are among the most enriched. Then we confirmed two candidates Enolase-1 (and NSE (Neuron-Specific Enolase) in brain) and PKM (Pyruvate Kinase Muscle) are associated with SIRT1 in brain tissue lysis by co-immunoprecipitation. Furthermore, increase or decrease the SIRT1 enzyme activity by its agonist SRT1720 or antagonist EX527 could significantly affect the acetylation level of endogenous NSE and PKM, SIRT1 overexpression or knock out expreiments also showed the same results as use SIRT1's agonist or antagonist. Moreover, the acetylation changes on NSE or PKM could finally lead to affection on their catalytic activity. Taken together, our findings suggest that the function of SIRT1 binding proteins is enriched in metabolic pathways. NSE and PKM are new SIRT1 binding molecules. SIRT1 may regulate acetylation level of NSE and PKM through deacetylation and further regulate their catalytic activity. Our study provides new evidence for the involvement of SIRT1 in the mechanisms of metabolic regulation in central nervous system.

Ehrlichia species in pond-farmed leeches (Hirudinaria sp.) in Hubei Province, China.

Leeches are frequently used in traditional Chinese medicine. However, they are potentially hazardous to human and animal health by transmitting several pathogens. Studies of diseases transmitted by leeches are scarce. The purpose of this study was to analyze the pathogens carried in pond-farmed medicinal leech in China. Leeches were collected from 6 farms in Hubei Province in central China. DNA was extracted from the internal organ of leeches to analyze the origin of blood meal. Leech genera were confirmed through amplification of 18S rRNA and mitochondrial gene cytochrome oxidase I (COI) gene by PCR and host animal species were identified through amplification of mitochondrial cytochrome b gene. Species of Ehrlichia in the leech specimens were screened with PCR using specific primers. PCR amplification and DNA sequencing showed that 620 leeches were Hirudinaria sp. Ehrlichia DNA was detected in 39 specimens from 2 farms. We obtained a total of 65 sequences of the cytB gene from 620 leech internal organ samples including sequences of human (n = 5), rat (n = 1), domestic pig (n = 10), duck (n = 23), goose (n = 12) and buffalo (n = 14). Phylogenetic analysis of the rrs and groEL gene sequences showed that Ehrlichia detected in the study were closely related to Ehrlichia sp. in ticks from Korea and Japan. To the best of our knowledge, this is the first report on Ehrlichia DNA being detected from leeches. Our findings provided new data on Ehrlichia spp. and farmed leech species in China.

Mechanisms of Nα-lauroyl arginate ethyl ester against Penicillium digitatum and Pectobacterium carotovorum subsp. carotovorum.

The purpose of this study was to investigate the antimicrobial activity and mechanisms of Nα-lauroyl arginate ethyl ester (LAE) against Penicillium digitatum and Pectobacterium carotovorum subsp. carotovorum. The minim inhibitory concentrations of LAE against P. digitatum and P. carotovorum were found to be 400 and 25 µg/ml, respectively. Loss of intracellular protein and nucleic acid increased significantly, and membrane permeability reached 76.28, 54.29 and 85.20%, respectively, when 400 µg/ml of LAE was applied to the hyphae and spores of P. digitatum and to P. carotovorum. Flow cytometry showed that LAE reduced the membrane potential, and the depolarization ratios of P. digitatum and P. carotovorum were 98.19 and 97.25% (P < 0.05), respectively. Transmission electron microscopy photos revealed that LAE caused a rough surface, irregular cellular organelles, protoplast shrinkage, intracytoplasmic coagulation and empty cavities in all three cell types. These results showed that LAE had notable ability to damage the structure of fungal and bacterial cells, making it a possible alternative chemical for use in the preservation of fruits and vegetables.

Inorganic lanthanides induce PCR bias towards shorter amplicons.

Rare earth elements have many uses, and are frequently included in products such as fluorescent materials, hydride batteries, catalytic materials and lasers. In this study, it was observed that trivalent lanthanide ions (Ln[III] ions) appeared to inhibit the synthesis of large fragments in PCR assays, thus resulting in the preferential amplification of shorter sequences. It is therefore speculated that this Ln(III) ion-mediated bias could be utilized to improve the success rates for amplification of shorter products.

Antityrosinase mechanism of omeprazole and its application on the preservation of fresh-cut Fuji apple.

Omeprazole was first evaluated for its antityrosinase activity and preservation of fresh-cut apples. The results obtained from enzymic analyses showed that the omeprazole inhibited tyrosinase activity (IC50 = 40 ±â€¯1.2 µM) with a reversible and competitive mechanism. Fluorescence quenching assays demonstrated that the interaction between omeprazole and tyrosinase was driven by hydrophobic forces and hydrogen bonds in a static procedure. Molecular docking further revealed that hydrogen bonds and hydrophobic forces were generated by omeprazole with the amino acid residues located in the A chain of tyrosinase. Moreover, the results from preservation assays showed that omeprazole could inhibit the activities of polyphenol oxidase (PPO) and peroxidase (POD), prevent the oxidation of total phenolics and flavonoid, thereby delay the browning of fresh-cut apples. Hence, this work identified a novel tyrosinase inhibitor and expands its feasible application as a food preservative.

Effects of Phytase Transgenic Maize on the Physiological and Biochemical Responses and the Gut Microflora Functional Diversity of Ostrinia furnacalis.

Transgenic maize hybrids that express the Aspergillus niger phyA2 gene could significantly improve phosphorus bioavailability to poultry and livestock. However, little information has been reported about the effects of phytase transgenic maize on the Asian corn borer (ACB), Ostrinia furnacalis (Guenée). This study provides valuable information about the physiological, biochemical and gut microflora functional diversity changes of ACBs fed phytase transgenic maize. The weights, survival rates, in vivo protein contents, activities of two detoxification enzymes and three antioxidant enzymes of ACBs fed phytase transgenic maize exhibited no significant differences to those fed non-transgenic maize. Functional diversities of the gut microflora communities of ACBs were not affected by different fodder treatments, but significant differences were observed between different generations of ACBs. Our study provides useful information about the biochemical responses and gut microflora community functional diversities of ACBs fed phytase transgenic maize firstly and the results will help to assess the potential effects of phytase transgenic maize on other target and non-target arthropods in the future.

Pterostilbene protects against uraemia serum-induced endothelial cell damage via activation of Keap1/Nrf2/HO-1 signaling.

Chronic kidney disease causes uremia-related endothelial cell dysfunction associated with high risk for cardiovascular diseases. The vascular endothelium is permanently exposed to uraemic toxins including indoxyl sulfate, which provokes endothelial damage in subjects with end-stage renal disease. Pterostilbene (PT) is identified to be homologous derivative of resveratrol and exerts antioxidant and anti-inflammatory actions. However, the effects of PT on uraemic serum-induced endothelial cell damage have not been elucidated. In this study, we investigated the effects and mechanisms of PT on uraemic serum (US)-mediated injury in human umbilical vein endothelial cells (HUVECs). Treatment of US obviously reduced cell viability, inhibited superoxide dismutase activity and catalase activity, suppressed phosphorylated endothelial nitric oxide synthase (eNOS) protein level and eNOS activity, whereas promoted lactate dehydrogenase leakage, increased malondialdehyde, hydrogen peroxide, superoxide anions levels and NAD(P)H activity accompanied with increased nitrative stress and inflammatory response in HUVECs, and these changes were reversed after PT treatment. Under US environment, PT downregulated Kelch-like ECH-associated protein 1 (Keap1) and upregulated nuclear factor erythroid-2-related factor 2 (Nrf2) and its downstream target heme oxygenase-1 (HO-1) protein levels. Of note, the level of HO-1 was decreased after the transfection of cells with Nrf2-siRNA, and HO-1 inhibitor Snpp abolished the protective effects of PT on HUVECs in response to US. Collectively, our study demonstrated that PT is effective in reducing US-evoked endothelial cell dysfunction via suppression of oxidative/nitrative stress and inflammatory response, which at least partly depended on Keap1/Nrf2/HO-1 signaling pathway.

MARCKS is Necessary for Oligodendrocyte Precursor Cell Maturation.

Oligodendrocyte precursor cell (OPC) development into myelinated oligodendrocytes demands vigorous membrane addition. Since myristoylated alanine-rich C-kinase substrate (MARCKS) reportedly contributes to Ras-associated protein (Rab)-10-associated vesicle insertion into neuronal membranes, we investigated the role of MARCKS in OPC maturation. We found that either knockdown of MARCKS or interruption of its interaction with Rab10 would cause a decrease of the cell membrane area during OPC development. Enhanced MARCKS phosphorylation by Nogo66 or myelin debris treatment inhibited OPC maturation, while its dephosphorylation by protein phosphatase 2 A activator D-erythro-sphingosine promoted OPC development in the presence of myelin debris. Our results demonstrated that MARCKS is involved in OPC maturation by interacting with Rab10.