Effect of Chemical Agents on the Morphology and Chemical Structures of Microplastics.

Increased demand for plastics leads to a large amount of plastic manufacturing, which is accompanied by inappropriate disposal of plastics. The by-products of these waste plastics are microplastics (MPs; less than 5 nm in size), which are produced because of various environmental and physicochemical factors, posing hazardous effects to the ecosystem, such as the death of marine organisms due to the swallowing of plastic specks of no nutritional value. Therefore, the collection, preparation, identification, and recycling of these microsized plastics have become imperative. The pretreatment of MPs requires numerous chemical agents comprising strong acids, bases, and oxidizing agents. However, there is limited research on the chemical resistance of various MPs to these substances to date. In this study, the chemical resistance of five species of MPs (high-density polyethylene, low-density polyethylene, polystyrene, polyethylene terephthalate, and polypropylene) to sulfuric acid, hydrochloric acid, hydrogen peroxide, potassium hydroxide, and sodium hydroxide was studied. The MPs were reacted with these chemical reagents at preset temperatures and durations, and variations in morphology and chemical structures were detected when the MPs were reacted with mineral acids, such as sulfuric acid. The data pertaining to these changes in MP properties could be a significant reference for future studies on MP pretreatment with strong acids, bases, and oxidizing agents.

Crosstalk between mucosal microbiota, host gene expression, and sociomedical factors in the progression of colorectal cancer.

Various omics-based biomarkers related to the occurrence, progression, and prognosis of colorectal cancer (CRC) have been identified. In this study, we attempted to identify gut microbiome-based biomarkers and detect their association with host gene expression in the initiation and progression of CRC by integrating analysis of the gut mucosal metagenome, RNA sequencing, and sociomedical factors. We performed metagenome and RNA sequencing on colonic mucosa samples from 13 patients with advanced CRC (ACRC), 10 patients with high-risk adenoma (HRA), and 7 normal control (NC) individuals. All participants completed a questionnaire on sociomedical factors. The interaction and correlation between changes in the microbiome and gene expression were assessed using bioinformatic analysis. When comparing HRA and NC samples, which can be considered to represent the process of tumor initiation, 28 genes and five microbiome species were analyzed with correlation plots. When comparing ACRC and HRA samples, which can be considered to represent the progression of CRC, seven bacterial species and 21 genes were analyzed. When comparing ACRC and NC samples, 16 genes and five bacterial species were analyzed, and four correlation plots were generated. A network visualizing the relationship between bacterial and host gene expression in the initiation and progression of CRC indicated that Clostridium spiroforme and Tyzzerella nexilis were hub bacteria in the development and progression of CRC. Our study revealed the interactions of and correlation between the colonic mucosal microbiome and host gene expression to identify potential roles of the microbiome in the initiation and progression of CRC. Our results provide gut microbiome-based biomarkers that may be potential diagnostic markers and therapeutic targets in patients with CRC.

High Expression of Claudin-4 Is Associated with Synchronous Tumors in Patients with Early Gastric Cancer.

Claudin (CLDN) is a tight junction protein found in human epithelial cells and its altered expression is known to be associated with the progression of gastric cancer. We aimed to investigate the differential expression of CLDN-4 in early gastric cancer (EGC) according to its clinicopathological characteristics. We enrolled 53 patients with EGC who underwent surgical gastric resection from January 2007 to December 2018. The staining intensity of the tumor cells was scored as 0-3, and the percentage of staining was scored as 0-5; high expression was defined if the intensity plus percentage score was 7 or 8, and low expression was defined if the score was 0-6. Among the 53 patients, 16 (30.2%) showed low CLDN-4 expression, while 37 (69.8%) had high CLDN-4 expression. High CLDN-4 expression was significantly associated with intestinal-type EGC (low: 12.5% vs. high: 56.8%, p = 0.003), open-type atrophic change (low: 60.0% vs. high: 90.9%, p = 0.011), and the presence of synchronous tumors (0 vs. 32.4%, p = 0.010), and all 12 EGCs with synchronous tumors showed high CLDN-4 expression. However, expression of CLDN-3, a typical intestinal phenotype CLDN, was neither correlated with CLDN-4 expression nor associated with synchronous tumors. Taken together, high CLDN-4 expression may be considered as an auxiliary tool for screening synchronous tumors in patients with EGC.

Detection of Microsatellite Instability in Colorectal Cancer Patients With a Plasma-Based Real-Time PCR Analysis.

A microsatellite instability (MSI) test is crucial for screening for HNPCC (Hereditary nonpolyposis colorectal cancer; Lynch syndrome) and optimization of colorectal cancer (CRC) treatment. Mismatch repair (MMR) deficiency is a predictor for good response of immune checkpoint inhibitors in various malignancies. In this study, we evaluated the results of a newly developed plasma-based real-time PCR kit for the detection of MSI in CRC patients. We assessed a peptide nucleotide acid (PNA) probe-mediated real-time PCR test (U-TOP MSI Detection Kit Plus) that determines MSI status by using amplicon melting analysis of five markers (NR21, NR24, NR27, BAT25, and BAT26) from plasma. Eighty-four CRC patients (46 dMMR and 38 pMMR) with colorectal cancer were analyzed. The concordance rate of MSI status assessment between the plasma kit and IHC was 63.0% in dMMR patients (29/46), but in the pMMR evaluation, a 100% (38/38) concordance rate was observed. In the evaluation of the performance of a custom tissue U-TOP MSI Detection Kit and plasma kit in 28 patients, sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value) of plasma kit were 68.4, 100, 100, and 44.4%, respectively, with the tissue U-TOP MSI Detection Kit. Our results demonstrate the feasibility of a non-invasive and rapid plasma-based real-time PCR kit (U-TOP MSI Detection Kit Plus) for the detection of MSI in colorectal cancer.

RNA-sequencing identification and validation of genes differentially expressed in high-risk adenoma, advanced colorectal cancer, and normal controls.

Distinct gene expression patterns that occur during the adenoma-carcinoma sequence need to be determined to analyze the underlying mechanism in each step of colorectal cancer progression. Elucidation of biomarkers for colorectal polyps that harbor malignancy potential is important for prevention of colorectal cancer. Here, we use RNA sequencing to determine gene expression profile in patients with high-risk adenoma treated with endoscopic submucosal dissection by comparing with gene expression in patients with advanced colorectal cancer and normal controls. We collected 70 samples, which consisted of 27 colorectal polyps, 24 cancer tissues, and 19 normal colorectal mucosa. RNA sequencing was performed on an Illumina platform to select differentially expressed genes (DEGs) between colorectal polyps and cancer, polyps and controls, and cancer and normal controls. The Kyoto Gene and Genome Encyclopedia (KEGG) and gene ontology (GO) analysis, gene-concept network, GSEA, and a decision tree were used to evaluate the DEGs. We selected the most highly expressed genes in high-risk polyps and validated their expression using real-time PCR and immunohistochemistry. Compared to patients with colorectal cancer, 82 upregulated and 24 downregulated genes were detected in high-risk adenoma. In comparison with normal controls, 33 upregulated and 79 downregulated genes were found in high-risk adenoma. In total, six genes were retrieved as the highest and second highest expressed in advanced polyps and cancers among the three groups. Among the six genes, ANAX3 and CD44 expression in real-time PCR for validation was in good accordance with RNA sequencing. We identified differential expression of mRNAs among high-risk adenoma, advanced colorectal cancer, and normal controls, including that of CD44 and ANXA3, suggesting that this cluster of genes as a marker of high-risk colorectal adenoma.

PARK7 maintains the stemness of glioblastoma stem cells by stabilizing epidermal growth factor receptor variant III.

PARK7 is involved in many key cellular processes, including cell proliferation, transcriptional regulation, cellular differentiation, oxidative stress protection, and mitochondrial function maintenance. Deregulation of PARK7 has been implicated in the pathogenesis of various human diseases, including cancer. Here, we aimed to clarify the effect of PARK7 on stemness and radioresistance of glioblastoma stem cells (GSCs). Serum differentiation and magnetic cell sorting of GSCs revealed that PARK7 was preferentially expressed in GSCs rather than differentiated GSCs. Immunohistochemical staining showed enhanced expression of PARK7 in glioma tissues compared to that in normal brain tissues. shRNA-mediated knockdown of PARK7 inhibited the self-renewal activity of GSCs in vitro, as evidenced by the results of neurosphere formation, limiting dilution, and soft-agar clonogenic assays. In addition, PARK7 knockdown suppressed GSC invasion and enhanced GSC sensitivity to ionizing radiation (IR). PARK7 knockdown suppressed expression of GSC signatures including nestin, epidermal growth factor receptor variant III (EGFRvIII), SOX2, NOTCH1, and OCT4. Contrarily, overexpression of PARK7 in CD133- non-GSCs increased self-renewal activities, migration, and IR resistance, and rescued the reduction of GSC factors under shPARK7-transfected and serum-differentiation conditions. Intriguingly, PARK7 acted as a co-chaperone of HSP90 by binding to it, protecting EGFRvIII from proteasomal degradation. Knockdown of PARK7 increased the production of reactive oxygen species, inducing partial apoptosis and enhancing IR sensitivity in GSCs. Finally, PARK7 knockdown increased mouse survival and IR sensitivity in vivo. Based on these data, we propose that PARK7 plays a pivotal role in the maintenance of stemness and therapeutic resistance in GSCs.

Ultralow Water Permeation Barrier Films of Triad a-SiNx:H/n-SiOxNy/h-SiOx Structure for Organic Light-Emitting Diodes.

Organic electronic devices such as organic light-emitting diodes (OLEDs), quantum dot LEDs, and organic photovoltaics are promising technologies for future electronics. However, achieving long-term stability of organic-based optoelectronic devices has been regarded as a crucial problem to be solved. In this work, a simple and reproducible fabrication method for ultralow water permeation barrier films having a triple-layered (triad) hydrogenated silicon nitride (a-SiNx:H)/nanosilicon oxynitride (n-SiOxNy)/hybrid silicon oxide (h-SiOx) multistructure is presented. Two triad (a-SiNx:H/n-SiOxNy/h-SiOx)n=2 multistructure barrier films are deposited on both sides of a poly(ethylene terephthalate) substrate using a combination of low-pressure plasma-enhanced chemical vapor deposition and dip coating. The deposited films show a high average transmittance (400-700 nm) of 84% and an ultralow water vapor transmission rate of 2 × 10-6 g/m2/day. In the electroluminescence characteristics of OLEDs encapsulated with two triad barrier films, the operational lifetime (T50) of OLEDs is 1584 h, which is almost similar to that (1416 h) of OLEDs encapsulated with a glass lid.

Intestinal Epithelial Deletion of Sphk1 Prevents Colitis-Associated Cancer Development by Inhibition of Epithelial STAT3 Activation.

BACKGROUND AND AIMS: Colitis-associated cancer (CAC) is one of the most serious complications in patients with inflammatory bowel disease. Sphingosine kinase 1 (Sphk1) is a key enzyme in the sphingolipid pathway and has oncogene potential for inducing both initiation and progression of tumors. The aim of this work is to characterize the role of epithelial Sphk1 in mouse colitis and CAC models. METHODS: We investigated the roles of Sphk1 in CAC by conditional deletion of Sphk1 in intestinal epithelial cells (IECs). RESULTS: CAC was induced in both Sphk1ΔIEC/ApcMin/+ and Sphk1IEC/ApcMin/+ mice by administration of 2% dextran sodium sulfate (DSS) for 7 days. Genetic deletion of Sphk1 significantly reduced the number and size of tumors in ApcMin/+ mice. Histologic grade was more severe in Sphk1ΔIEC/ApcMin/+ mice compared with Sphk1IEC/ApcMin/+ mice (invasive carcinoma, 71% versus 13%, p < 0.05). Deletion of Sphk1 decreased mucosal proliferation and inhibited STAT3 activation and genetic expression of cyclin D1 and cMyc in tumor cells. Conditional deletion of Sphk1 using CRISPR-Cas9 in HCT 116 cells inhibited interleukin (IL)-6-mediated STAT3 activation. CONCLUSIONS: Epithelial conditional deletion of Sphk1 inhibits CAC in ApcMin/+-DSS models in mice by inhibiting STAT3 activation and its target signaling pathways.

MW-PPG Sensor: An on-Chip Spectrometer Approach.

Multi-wavelength photoplethysmography (MW-PPG) sensing technology has been known to be superior to signal-wavelength photoplethysmography (SW-PPG) sensing technology. However, limited by the availability of sensing detectors, many prior studies can only use conventional bulky and pricy spectrometers as the detectors, and hence cannot bring the MW-PPG technology to daily-life applications. In this study we developed a chip-scale MW-PPG sensor using innovative on-chip spectrometers, aimed at wearable applications. Also in this paper we present signal processing methods for robustly extracting the PPG signals, in which an increase of up to 50% in the signal-to-noise ratio (S/N) was observed. Example measurements of saturation of peripheral blood oxygen (SpO2) and blood pressure were conducted.

Early differentiation of long-standing persistent atrial fibrillation using the characteristics of fibrillatory waves in surface ECG multi-leads.

We characterized the f-waves in atrial fibrillation (AF) in the surface ECG by quantifying the amplitude, irregularity, and dominant rate of the f-waves in leads II, aVL, and V1, and investigated whether those parameters of the f-waves could discriminate long-standing persistent AF (LPeAF) from non-LPeAF. A total of 224 AF patients were enrolled: 112 with PAF (87 males), 48 with PeAF (38 males), and 64 with LPeAF (47 males). The f-waves in surface ECG leads V1, aVL, and II, which reflect well electrical activity in the right atrium (RA), the left atrium (LA), and both atria, respectively, were analyzed. The f-waves for LPeAF had lower amplitudes in II and aVL, increased irregularity and a higher dominant rate in II and V1 compared to PAF and PeAF (all p < 0.02). In a multivariate analysis, a low amplitude in lead II (<34.6 uV) and high dominant rate in lead V1 (≧390/min) (p < 0.001) independently discriminated LPeAF from the other AF types. The f-waves combined with both a low amplitude in lead II and high dominant rate in lead V1 were significantly associated with LPeAF (OR 6.27, p < 0.001). Characteristics of the f-waves on the surface ECG could discriminate LPeAF from other types of AF.

PKA-dependent phosphorylation of IP3K-A at Ser119 regulates a binding affinity with EB3.

Microtubule-associated end-binding protein 3 (EB3) accumulates asymmetrically at the tip-end of growing microtubules, providing a central platform for linking various cellular components. EB3 orchestrates microtubule dynamics and targeting, enabling diverse processes within neurons. Inositol 1, 4, 5-trisphosphate 3-kinase A (IP3K-A; also known as ITPKA) is a neuron-enriched protein that binds to microtubules by PKA-dependent manners. In this study, we found that IP3K-A binds to EB3 and their binding affinity is precisely regulated by protein kinase A (PKA)-dependent phosphorylation of IP3K-A at Ser119 (pSer119). We also revealed that the complex of IP3K-A and EB3 dissociates and reassociates rapidly during chemically induced LTP (cLTP) condition. This dynamic rearrangement of IP3K-A and EB3 complex will contribute remodeling of microtubule cytoskeleton allowing effective structural plasticity in response to synaptic stimulations.

Efficacy and safety of thread embedding acupuncture for chronic low back pain: a randomized controlled pilot trial.

BACKGROUND: We investigated the efficacy and safety of thread-embedding acupuncture (TEA) for chronic low back pain (LBP) in a randomized controlled pilot trial with the aim of laying the foundation for a large-scale randomized controlled trial on this topic. METHODS: Forty participants were recruited for this two-arm, assessor-blinded randomized controlled pilot trial. The participants were randomly allocated to a TEA group (experimental group) or an acupuncture group (control group). The TEA group received TEA once every 2 weeks for 8 weeks (four sessions in total), while the acupuncture group received acupuncture twice per week for 8 weeks (16 sessions in total). The primary outcome was the visual analog scale (VAS) score for pain and the secondary outcomes were short-form McGill Pain Questionnaire (SF-MPQ) and Oswestry Disability Index (ODI) scores. Assessments were performed at screening and at 2, 4, 6, 8, and 10 weeks after treatment initiation (the 10-week assessment was conducted at 2 weeks after treatment cessation). RESULTS: Of the 40 participants, 36 completed the study and four dropped out. Both the TEA group and the acupuncture group showed significant improvements in VAS, SF-MPQ, and ODI scores in a time-dependent manner. Furthermore, with regard to ODI, a significant interaction between group and time was observed, with the two groups exhibiting a different pattern of change at 8 weeks according to contrast analysis with Bonferroni's correction. No serious adverse event occurred, and hematological and biochemical test findings were within normal limits. CONCLUSION: This pilot study has provided basic data for a larger clinical trial to demonstrate the efficacy and safety of TEA for chronic LBP. TRIAL REGISTRATION: Clinical Research Information Service of the Korea National Institute of Health, ID: KCT0001819 . Registered on 15 February 2016.

Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer.

BACKGROUND: We investigated the inhibitory effect of pantoprazole on signal transducer and activator of transcription 3 (STAT3) activity and invasiveness of gastric adenocarcinoma cells, and the role of SH2-containing protein tyrosine phosphatase 1 (SHP-1) in mediating role. METHODS: We used AGS and MKN-28 cells because of reduced SHP-1 and preserved p-STAT3 expression. Western blot, wound closure assay, Matrigel invasion assay and 3-D culture invasion assay were performed. Pharmacologic inhibitor of SHP-1 and siRNA were used for validation of the role of SHP-1. RESULTS: We observed that pantoprazole at 40, 80, and 160 µg/ml upregulated SHP-1 and downregulated p-STAT3 expression in a dose-dependent manner in AGS and MKN-28 cells. Furthermore, pantoprazole significantly downregulated mesenchymal markers (Snail1 and vimentin), upregulated epithelial marker (E-cadherin), and inhibited migration and invasion of AGS and MKN-28 cells. To validate the role of SHP-1 in inhibition of STAT3 activity by pantoprazole in gastric cancer cells, we performed pharmacologic inhibition (pervanadate) or knockdown of SHP-1 before pantoprazole treatment, which significantly attenuated the suppression of p-STAT3 and anti-migration and invasion effect by pantoprazole in AGS cells. In xenograft tumor model, tumor volume was significantly reduced by intraperitoneal injection of pantoprazole, with upregulation of SHP-1 and downregulation of p-STAT3, which were attenuated by concomitant injection of pervanadate. CONCLUSION: Our data suggest that the inhibitory effect of pantoprazole on cellular migration and invasion might be through inducing SHP-1 in gastric cancer cells.

The relationship between coronary atherosclerosis and body fat distribution measured using dual energy X-ray absorptiometry.

OBJECTIVE: Body fat distribution is closely related to cardiovascular diseases. We aimed to evaluate the relationship between truncal fat distribution and the extent of coronary atherosclerosis. METHODS: Total body fat and regional body fat distributions were measured using dual-energy X-ray absorptiometry (DXA) in 746 Korean patients who underwent coronary angiography. The ratios of truncal fat mass to total body fat mass (FMtrunk/FMtotal), truncal fat mass to fat mass in both legs (FMtrunk/FMleg) and truncal fat mass to fat mass in both arms (FMtrunk/FMarm) were calculated as representative parameters for truncal fat accumulation. The extent of coronary atherosclerosis was assessed using the Gensini score. RESULTS: The mean Gensini score of the patients was 21.3 ± 24.4. FMtrunk/FMtotal, FMtrunk/FMleg and FMtrunk/FMarm revealed positive correlations with the Gensini score (r = 0.242, p < 0.001; r = 0.219, p < 0.001; r = 0.133, p < 0.001, respectively). In contrast, body mass index (BMI) and total body fat mass did not correlate with the Gensini score. On multiple regression analysis, FMtrunk/FMtotal was associated with the Gensini score independently of age, gender, BMI and major risk factors of coronary heart disease (B = 0.039, p < 0.001). CONCLUSION: Truncal fat distribution is associated with the extent of coronary atherosclerosis and more clinically relevant to that compared with total body fat or BMI in Korean patients.

A Case of Incus Vibroplasty: Postoperative Changes in Residual Hearing.

In patients with mild to severe hearing loss, conventional hearing aids offer limited benefits and several problems with feedback and cosmesis. Middle ear implants are a feasible option for patients with moderate to severe hearing loss who are unable to achieve adequate benefit from or cannot tolerate hearing aids for various reasons. Here we present a case of middle ear implant surgery using Vibrant Soundbridge with incus vibroplasty technique, and describe the hearing changes during postoperative follow-up.

PGD2 deficiency exacerbates food antigen-induced mast cell hyperplasia.

Prostaglandin D2 (PGD2) is a major prostanoid secreted mainly by mast cells. Although PGD2 has been identified as a modulator of allergic inflammation, its precise role remains unclear. Here we investigate the role of PGD2 in food allergy. Oral administration of ovalbumin induces allergic responses in sensitized wild-type (WT) mice. Systemic gene deficiency of haematopoietic PGD synthase (H-PGDS(-/-)) exacerbates all of the manifestations accompanying severe mast cell hyperplasia in the intestine. Morphological studies show that c-kit/FcɛRI-positive WT mast cells strongly express H-PGDS. Transplantation of H-PGDS(-/-) mast cells also aggravates ovalbumin-induced mast cell hyperplasia and allergic symptoms in mast cell null mice. H-PGDS deficiency accelerates the production of SDF-1α and the activity of MMP-9 in the antigen-stimulated intestine. SDF-1α receptor blockade or MMP-9 inhibition relieves the exacerbated mast cell hyperplasia and manifestations observed in H-PGDS(-/-). Thus, PGD2 deficiency results in food antigen-induced mast cell hyperplasia.

Fetal hematopoietic stem cells express MFG-E8 during mouse embryogenesis.

The milk fat globule-EGF-factor 8 protein (MFG-E8) has been identified in various tissues, where it has an important role in intercellular interactions, cellular migration, and neovascularization. Previous studies showed that MFG-E8 is expressed in different cell types under normal and pathophysiological conditions, but its expression in hematopoietic stem cells (HSCs) during hematopoiesis has not been reported. In the present study, we investigated MFG-E8 expression in multiple hematopoietic tissues at different stages of mouse embryogenesis. Using immunohistochemistry, we showed that MFG-E8 was specifically expressed in CD34(+) HSCs at all hematopoietic sites, including the yolk sac, aorta-gonad-mesonephros region, placenta and fetal liver, during embryogenesis. Fluorescence-activated cell sorting and polymerase chain reaction analyses demonstrated that CD34(+) cells, purified from the fetal liver, expressed additional HSC markers, c-Kit and Sca-1, and that these CD34(+) cells, but not CD34(-) cells, highly expressed MFG-E8. We also found that MFG-E8 was not expressed in HSCs in adult mouse bone marrow, and that its expression was confined to F4/80(+) macrophages. Together, this study demonstrates, for the first time, that MFG-8 is expressed in fetal HSC populations, and that MFG-E8 may have a role in embryonic hematopoiesis.

CCR8 regulates contact hypersensitivity by restricting cutaneous dendritic cell migration to the draining lymph nodes.

Allergic contact dermatitis (ACD) is a typical occupational disease in industrialized countries. Although various cytokines and chemokines are suggested to be involved in the pathogenesis of ACD, the roles of these molecules remain to be elucidated. CC chemokine receptor 8 (CCR8) is one such molecule, of which expression is up-regulated in inflammatory sites of ACD patients. In this study, we found that Ccr8(-/-) mice developed severer contact hypersensitivity (CHS) responses to 2,4-dinitrofluorobenzene, a murine model of ACD, compared with wild-type mice. T cells from Ccr8(-/-) mice showed enhanced proliferative recall responses and Th1 and Th17 cell populations were expanded in these mice. However, CHS responses were similar between SCID mice adoptively transferred with Ccr8(-/-) and wild-type T cells, suggesting that CCR8 in T cells is not responsible for the exacerbation of CHS. Notably, skin-resident dendritic cells (DCs), such as Langerhans cells and dermal DCs, and inflammatory DCs were highly accumulated in lymph nodes (LNs) of Ccr8(-/-) mice after sensitization. Consistent with this, Ccr8(-/-) antigen-presenting cells readily migrated from the skin to the draining LNs after sensitization. These observations suggest that CCR8 negatively regulates migration of cutaneous DCs from the skin to the draining LNs in CHS by keeping these cells in the skin.

Inositol 1,4,5-trisphosphate 3-kinase A is a novel microtubule-associated protein: PKA-dependent phosphoregulation of microtubule binding affinity.

Inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A) is a brain specific and F-actin-binding protein. We recently demonstrated that IP(3)K-A modulates a structural reorganization of dendritic spines through F-actin remodeling, which is required for synaptic plasticity and memory formation in brain. However, detailed functions of IP(3)K-A and its regulatory mechanisms involved in the neuronal cytoskeletal dynamics still remain unknown. In the present study, we identified tubulin as a candidate of IP(3)K-A-binding protein through proteomic screening. By various in vitro and in vivo approaches, we demonstrated that IP(3)K-A was a novel microtubule-associated protein (MAP), and the N terminus of IP(3)K-A was a critical region for direct binding to tubulin in dendritic shaft of hippocampal neurons. Moreover, PKA phosphorylated Ser-119 within IP(3)K-A, leading to a significant reduction of microtubule binding affinity. These results suggest that PKA-dependent phosphorylation and microtubule binding of IP(3)K-A are involved in its regulatory mechanism for activity-dependent neuronal events such as local calcium signaling and its synaptic targeting.