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1.  Angular and temperature dependence of current induced spin-orbit effective fields in Ta/CoFeB/MgO nanowires 
Scientific Reports  2014;4:4491.
Current induced spin-orbit effective magnetic fields in metal/ferromagnet/oxide trilayers provide a new way to manipulate the magnetization, which is an alternative to the conventional current induced spin transfer torque arising from noncollinear magnetization. Ta/CoFeB/MgO structures are expected to be useful for non-volatile memories and logic devices due to its perpendicular anisotropy and large current induced spin-orbit effective fields. However many aspects such as the angular and temperature dependent phenomena of the effective fields are little understood. Here, we evaluate the angular and temperature dependence of the current-induced spin-orbit effective fields considering contributions from both the anomalous and planar Hall effects. The longitudinal and transverse components of effective fields are found to have strong angular dependence on the magnetization direction at 300 K. The transverse field decreases significantly with decreasing temperature, whereas the longitudinal field shows weaker temperature dependence. Our results reveal important features and provide an opportunity for a more comprehensive understanding of current induced spin-orbit effective fields.
doi:10.1038/srep04491
PMCID: PMC3967151  PMID: 24670317
2.  Eagle's syndrome: a case report 
Eagle's syndrome is a disease caused by an elongated styloid process or calcified stylohyoid ligament. Eagle defined the disorder in 1937 by describing clinical findings related to an elongated styloid process, which is one of the numerous causes of pain in the craniofacial and cervical region. The prevalence of individuals with this anatomic abnormality in the adult population is estimated to be 4% with 0.16% of these individuals reported to be symptomatic. Eagle's syndrome is usually characterized by neck, throat, or ear pain; pharyngeal foreign body sensation; dysphagia; pain upon head movement; and headache. The diagnosis of Eagle's syndrome must be made in association with data from the clinical history, physical examination, and imaging studies. Patients with increased symptom severity require surgical excision of the styloid process, which can be performed through an intraoral or an extraoral approach. Here, we report a rare case of stylohyoid ligament bilaterally elongated to more than 60 mm in a 51-year-old female. We did a surgery by extraoral approach and patient's symptom was improved.
doi:10.5125/jkaoms.2014.40.1.43
PMCID: PMC3949492  PMID: 24627843
Eagle syndrome; Elongated styloid process
3.  Retrospective clinical study of mandible fractures 
Objectives
The purpose of this article is to analyze the incidence, demographic distribution, type, and etiology of mandible fractures that were treated by the Department of Oral and Maxillofacial Surgery in Kyung Hee University Dental Hospital from January 2002 to December 2012.
Materials and Methods
This was a descriptive and analytic retrospective study that evaluated 735 patients that were treated for mandible fracture.
Results
This study included 1,172 fractures in 735 patients. The ratio of male to female patients was 5.45 : 1; the maximum value was in patients between 20 and 29 years (38.1%) and the minimum in patients over 70 years old. The monthly distribution of facial fractures peaked in the fall and was lower during winter. No specific correlation was identified based on the annual fracture distribution. Among the 735 fracture patients, 1.59 fracture lines were observed per patient. The most frequent site was the symphysis, which accounted for a total of 431 fractures, followed by the angle (348), condyle (279), and body (95). The symphysis with angle was the most common site identified in combination with fracture and accounted for 22.4%, followed by symphysis with condyle (19.8%). The angle was the most frequent site of single fractures (20.8%). The major cause of injury was accidental trauma (43.4%), which was followed by other causes such as violence (33.9%), sports-related accidents (10.5%), and traffic accidents (10.1%). Fracture incidents correlated with alcohol consumption were reported between 10.0%-26.9% annually.
Conclusion
Although mandible fracture pattern is similar to the previous researches, there is some changes in the etiologic factors.
doi:10.5125/jkaoms.2014.40.1.21
PMCID: PMC3949494  PMID: 24627839
Mandible; Jaw fractures; Mandibular fractures; Alcohol drinking; Trauma
4.  Impaired Extinction of Learned Contextual Fear Memory in Early Growth Response 1 Knockout Mice 
Molecules and Cells  2014;37(1):24-30.
Inductive expression of early growth response 1 (Egr-1) in neurons is associated with many forms of neuronal activity. However, only a few Egr-1 target genes are known in the brain. The results of this study demonstrate that Egr-1 knockout (KO) mice display impaired contextual extinction learning and normal fear acquisition relative to wild-type (WT) control animals. Genome-wide microarray experiments revealed 368 differentially expressed genes in the hippocampus of Egr-1 WT exposed to different phases of a fear conditioning paradigm compared to gene expression profiles in the hippocampus of KO mice. Some of genes, such as serotonin receptor 2C (Htr2c), neuropeptide B (Npb), neuronal PAS domain protein 4 (Npas4), NPY receptor Y1 (Npy1r), fatty acid binding protein 7 (Fabp7), and neuropeptide Y (Npy) are known to regulate processing of fearful memories, and promoter analyses demonstrated that several of these genes contained Egr-1 binding sites. This study provides a useful list of potential Egr-1 target genes which may be regulated during fear memory processing.
doi:10.14348/molcells.2014.2206
PMCID: PMC3907009  PMID: 24552706
contextual fear conditioning; Egr-1; extinction; hippocampus; microarray
5.  Measurement of Critical Structures around Paraclinoidal Area : A Cadaveric Morphometric Study 
Objective
Although removal of the anterior clinoid process (ACP) is essential surgical technique, studies about quantitative measurements of the space broadening by the anterior clinoidectomy are rare. The purposes of this study are to investigate the dimension of the ACP, to quantify the improved exposure of the parasellar space after extradural anterior clinoidectomy and to measure the correlation of each structure around the paraclinoidal area.
Methods
Eleven formalin-fixed Korean adult cadaveric heads were used and frontotemporal craniotomies were done bilaterally. The length of C6 segment of the internal carotid artery on its lateral and medial side and optic nerve length were checked before and after anterior clinoidectomy. The basal width and height of the ACP were measured. The relationships among the paraclinoidal structures were assessed. The origin and projection of the ophthalmic artery (OA) were investigated.
Results
The mean values of intradural basal width and height of the ACP were 10.82 mm and 7.61 mm respectively. The mean length of the C6 lateral and medial side increased 49%. The mean length of optic nerve increased 97%. At the parasellar area, the lengths from the optic strut to the falciform liament, distal dural ring, origin of OA were 6.69 mm, 9.36 mm and 5.99 mm, respectively. The distance between CN III and IV was 11.06 mm.
Conclusion
With the removal of ACP, exposure of the C6 segments and optic nerve can expand 49% and 97%, respectively. This technique should be among a surgeon's essential skills for treating lesions around the parasellar area.
doi:10.3340/jkns.2013.54.1.14
PMCID: PMC3772280  PMID: 24044074
Anterior clinoid process; Extradural anterior clinoidectomy; Optic strut; Ophthalmic segment
6.  High-efficiency tooth bleaching using non-thermal atmospheric pressure plasma with low concentration of hydrogen peroxide 
Journal of Applied Oral Science  2013;21(3):265-270.
Light-activated tooth bleaching with a high hydrogen peroxide (HP; H2O2) concentration has risks and the actual role of the light source is doubtful. The use of conventional light might result in an increase in the temperature and cause thermal damage to the health of the tooth tissue.
Objective:
This study investigated the efficacy of tooth bleaching using non-thermal atmospheric pressure plasma (NAPP) with 15% carbamide peroxide (CP; CH6N2O3) including 5.4% HP, as compared with conventional light sources.
Material and Methods:
Forty human teeth were randomly divided into four groups: Group I (CP+NAPP), Group II (CP+plasma arc lamp; PAC), Group III (CP+diode laser), and Group IV (CP alone). Color changes (ΔE ) of the tooth and tooth surface temperatures were measured. Data were evaluated by one-way analysis of variance (ANOVA) and post-hoc Tukey's tests.
Results:
Group I showed the highest bleaching efficacy, with a ΔE value of 1.92-, 2.61 and 2.97-fold greater than those of Groups II, III and IV, respectively (P<0.05). The tooth surface temperature was maintained around 37ºC in Group I, but it reached 43ºC in Groups II and III.
Conclusions:
The NAPP has a greater capability for effective tooth bleaching than conventional light sources with a low concentration of HP without causing thermal damage. Tooth bleaching using NAPP can become a major technique for in-office bleaching in the near future.
doi:10.1590/1679-775720130016
PMCID: PMC3881910  PMID: 23857658
Tooth bleaching; Plasma gases; Hydrogen peroxide; Temperature
7.  Patterns of Brain Atrophy in Clinical Variants of Frontotemporal Lobar Degeneration 
Background/Aims
The clinical syndromes of frontotemporal lobar degeneration include behavioral variant frontotemporal dementia (bvFTD) and semantic (SV-PPA) and nonfluent variants (NF-PPA) of primary progressive aphasia. Using magnetic resonance imaging (MRI), tensor-based morphometry (TBM) was used to determine distinct patterns of atrophy between these three clinical groups.
Methods
Twenty-seven participants diagnosed with bvFTD, 16 with SV-PPA, and 19 with NF-PPA received baseline and follow-up MRI scans approximately 1 year apart. TBM was used to create three-dimensional Jacobian maps of local brain atrophy rates for individual subjects.
Results
Regional analyses were performed on the three-dimensional maps and direct comparisons between groups (corrected for multiple comparisons using permutation tests) revealed significantly greater frontal lobe and frontal white matter atrophy in the bvFTD relative to the SV-PPA group (p < 0.005). The SV-PPA subjects exhibited significantly greater atrophy than the bvFTD in the fusiform gyrus (p = 0.007). The NF-PPA group showed significantly more atrophy in the parietal lobes relative to both bvFTD and SV-PPA groups (p < 0.05). Percent volume change in ventromedial prefrontal cortex was significantly associated with baseline behavioral symptomatology.
Conclusion
The bvFTD, SV-PPA, and NF-PPA groups displayed distinct patterns of progressive atrophy over a 1-year period that correspond well to the behavioral disturbances characteristic of the clinical syndromes. More specifically, the bvFTD group showed significant white matter contraction and presence of behavioral symptoms at baseline predicted significant volume loss of the ventromedial prefrontal cortex.
doi:10.1159/000345523
PMCID: PMC3609420  PMID: 23306166
Frontotemporal dementia; Primary progressive aphasia; Longitudinal study; Magnetic resonance imaging; Tensor-based morphometry; White matter
8.  Current routine practice and clinico-pathological characteristics associated with acute promyelocytic leukemia in Korea 
Blood research  2013;48(1):31-34.
Background
Acute promyelocytic leukemia (APL) can be life threatening, necessitating emergency therapy with prompt diagnosis by morphologic findings, immunophenotyping, cytogenetic analysis, or molecular studies. This study aimed to assess the current routine practices in APL and the clinico-pathologic features of APL.
Methods
We reviewed the medical records of 48 Korean patients (25 men, 23 women; median age, 51 (20-80) years) diagnosed with APL in 5 university hospitals between March 2007 and February 2012.
Results
The WBC count at diagnosis and platelet count varied from 0.4 to 81.0 (median 2.0)×109/L and 2.7 to 124.0 (median 54.5)×109/L, respectively. The median values for prothrombin time and activated partial thromboplastin time were 14.7 (11.3-44.1) s and 29 (24-62) s, respectively. All but 2 patients (96%) showed a fibrin/fibrinogen degradation product value of >20 µg/mL. The D-dimer median value was 5,000 (686-55,630) ng/mL. The t(15;17)(q22;q12 and PML-RARA fusion was found in all patients by chromosome analysis and/or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), with turnaround times of 8 (2-19) d and 7 (2-13) d, respectively. All patients received induction chemotherapy: all-trans retinoic acid (ATRA) alone (N=11, 26%), ATRA+idarubicin (N=25, 58%), ATRA+cytarabine (N=3, 7%), ATRA+idarubicin+cytarabine (N=4, 9%).
Conclusion
Since APL is a medical emergency and an accurate diagnosis is a prerequisite for prompt treatment, laboratory support to implement faster diagnostic tools to confirm the presence of PML-RARA is required.
doi:10.5045/br.2013.48.1.31
PMCID: PMC3625006  PMID: 23589792
Acute promyelocytic leukemia; PML-RARA; Immunophenotyping; Cytogenetic analysis; All-trans retinoic acid
9.  Galectin-3 increases the motility of mouse melanoma cells by regulating matrix metalloproteinase-1 expression 
Experimental & Molecular Medicine  2012;44(6):387-393.
Although mounting evidence indicates the involvement of galectin-3 in cancer progression and metastasis, the underlying molecular mechanisms remain largely unknown. In this study, we investigated the effect and possible mechanism of galectin-3 on the migration and invasion of B16F10, a metastatic melanoma cell line, in which galectin-3 and matrix metalloproteinase-1 (MMP-1) were both found to be highly expressed. Knockdown of galectin-3 with specific siRNA reduced migration and invasion, which was associated with reduced expression of MMP-1. To further investigate the underlying mechanism, we examined the effect of galectin-3 knockdown on the activity of AP-1, a transcriptional factor regulating MMP-1 expression. We found that galectin-3 directly interacted with AP-1 and facilitated the binding of this complex to the MMP-1 promoter that drives MMP-1 transcription. Moreover, silencing of galectin-3 inhibited binding of fra-1 and c-Jun to promoter sites of MMP-1 gene. Consistent with these in vitro findings, our in vivo study demonstrated that galectin-3 shRNA treatment significantly reduced the total number of mouse lung metastatic nodules. Taken together, galectin-3 facilitates cell migration and invasion in melanoma in vitro and can induce metastasis in vivo, in part through, regulating the transcription activity of AP-1 and thereby up-regulating MMP-1 expression.
doi:10.3858/emm.2012.44.6.044
PMCID: PMC3389077  PMID: 22437631
galectin 3; matrix metalloproteinase 1; melanoma; neoplasm metastasis; RNA, small interfering; transcription factor AP-1
10.  Identification of a shared F8 mutation in the Korean patients with acquired hemophilia A 
Although uncommon, acquired hemophilia A (HA) is associated with a high rate of mortality due to severe bleeding. In spite of many hypotheses regarding the cause of acquired HA, there is as yet no established theory. In this study, we investigated the possibility that mutation(s) in the F8 gene may be correlated with the development of inhibitory autoantibodies. Direct sequencing analysis was performed on all 26 exons of the F8 gene of 2 patients exhibiting acquired HA. Both patients were found to share a common point mutation (c.8899G>A) in the 3'-untranslated region (3'-UTR) of exon 26. This is the first report on the genotyping of F8 in the context of acquired HA.
doi:10.5045/kjh.2011.46.1.49
PMCID: PMC3065628  PMID: 21461305
Haemophilia A; Mutation profiling; Sequence variation; Acquired haemophilia A
11.  Spontaneous Contractions Augmented by Cholinergic and Adrenergic Systems in the Human Ureter 
Interstitial cells of Cajal (ICC) evoke pacemaker activities in many tissues. The purpose of this study was to investigate the relationship between interstitial cell and pacemaker activity in the human ureter through the recording of spontaneous contractions. Spontaneous contractions of eight circular and longitudinal smooth muscle strips of the human ureter to acetylcholine (ACh) and/or norepinephrine (NE) were observed. Human ureteral strips were divided into proximal and distal groups, and each group was subdivided into circular and longitudinal groups. The proximal group showed spontaneous activities of 3~4 times within 5 minutes in the longitudinal group. ACh (10-4 M) augmented the frequency of the spontaneous contractions. The cumulative application of NE also augmented the frequency in a dose-dependent manner. The effects of NE application were inhibited by concomitant application of 10-5 M glibenclamide. Receptor tyrosine kinase (c-kit) staining revealed abundant ICCs only in proximal tissues. Therefore, spontaneous contractions of the human ureter might be modulated by ICC in the proximal region, and the actions might be related with the activation of cholinergic and/or adrenergic system mediated by a glibenclamide-sensitive pathway.
doi:10.4196/kjpp.2011.15.1.37
PMCID: PMC3062082  PMID: 21461239
Interstitial cell of Cajal; Pacemaker activity; Spontaneous contraction; Human ureter
12.  Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans 
PPAR Research  2010;2009:867678.
Tumor suppressor candidate 5 (TUSC5) is a gene expressed abundantly in white adipose tissue (WAT), brown adipose tissue (BAT), and peripheral afferent neurons. Strong adipocyte expression and increased expression following peroxisome proliferator activated receptor γ (PPARγ) agonist treatment of 3T3-L1 adipocytes suggested a role for Tusc5 in fat cell proliferation and/or metabolism. However, the regulation of Tusc5 in WAT and its potential association with obesity phenotypes remain unclear. We tested the hypothesis that the TUSC5 gene is a bona fide PPARγ target and evaluated whether its WAT expression or single-nucleotide polymorphisms (SNPs) in the TUSC5 coding region are associated with human obesity. Induction of Tusc5 mRNA levels in 3T3-L1 adipocytes by troglitazone and GW1929 followed a dose-response consistent with these agents' binding affinities for PPARγ. Chromatin immunoprecipitation (ChIP) experiments confirmed that PPARγ protein binds a ∼ −1.1 kb promotor sequence of murine TUSC5 transiently during 3T3-L1 adipogenesis, concurrent with histone H3 acetylation. No change in Tusc5 mRNA or protein levels was evident in type 2 diabetic patients treated with pioglitazone. Tusc5 expression was not induced appreciably in liver preparations overexpressing PPARs, suggesting that tissue-specific factors regulate PPARγ responsiveness of the TUSC5 gene. Finally, we observed no differences in Tusc5 WAT expression or prevalence of coding region SNPs in lean versus obese human subjects. These studies firmly establish the murine TUSC5 gene locus as a PPARγ target, but the significance of Tusc5 in obesity phenotypes or in the pharmacologic actions of PPARγ agonists in humans remains equivocal.
doi:10.1155/2009/867678
PMCID: PMC2830574  PMID: 20204174
13.  A case of donor-derived granulocytic sarcoma after allogeneic hematopoietic stem cell transplantation 
The occurrence of granulocytic sarcoma as a pattern of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare. In this paper, we report a rare case of acute myeloid leukemia (AML) relapsed as a granulocytic sarcoma of the donor type. The patient was diagnosed as having AML and underwent an allo-HSCT from his matched sibling donor. Fifty-seven months after allo-HSCT, he developed granulocytic sarcomas of duodenum, jejunum, and left sterno-cleido-mastoid muscle. The bone marrow was normal with 100% donor chimerism. A Y chromosome PCR was performed on the patient's duodenum specimen as well as bone marrow aspirate in order to check the patient-origin cells. The duodenal specimen was found to contain 41.2% SRY-positive cells (from the donor). Repeat endoscopy on day 2 of chemotherapy showed that the granulocytic sarcoma had shrunk dramatically. The patient died of sepsis during the nadir state 35 days after starting salvage chemotherapy.
doi:10.5045/kjh.2010.45.1.70
PMCID: PMC2982999  PMID: 21120167
Granulocytic sarcoma; AML; Allo-HSCT; Donor type
14.  Low Expression of Bax Predicts Poor Prognosis in Resected Non-small Cell Lung Cancer Patients with Non-squamous Histology† 
Objective
The present study evaluated the prognostic significance of apoptosis-related proteins p53, Bax and galectin-3 in patients with non-small cell lung cancer (NSCLC) treated with surgical resection.
Methods
We investigated the expression of these proteins and their association with clinicopathologic characteristics including disease-free survival (DFS) and overall survival (OS) in 205 NSCLC patients who underwent surgical resection (Stage I, 97; II, 46; IIIA, 45; IIIB, 17) using immunohistochemistry. Eighty-eight patients (43%) received adjuvant treatment (chemotherapy: 8, radiotherapy: 24, both: 56).
Results
High expressions of Bax, p53 and galectin-3 were observed in 48 (23%), 81 (40%) and 105 (51%) patients, respectively. Low expression of Bax was significantly associated with male gender, squamous cell histology and low expression of galectin-3. Five-year DFS and OS of total patients were 37 and 46%, respectively. High expressions of p53 and galectin-3 were not associated with poor DFS or OS, and no significant correlation existed between low expression of Bax and outcome of patients. However, in patients with non-squamous histology (108 patients), low expression of Bax was a significant independent predictor of poor DFS (P = 0.017) and OS (P = 0.037). In addition, in patients with Stage II or III disease, low expression of Bax significantly correlated with poor DFS (P = 0.004). It was also the most significant independent poor prognostic factor second only to a large primary tumor size in Stage II or III patients with non-squamous histology.
Conclusions
Low expression of Bax was significantly associated with poor prognosis in resected NSCLC patients with non-squamous histology.
doi:10.1093/jjco/hyn089
PMCID: PMC2565351  PMID: 18772168
non-small cell lung cancer; Bax; prognosis
15.  Spontaneous Ligamentum Flavum Hematoma in the Rigid Thoracic Spine : A Case Report and Review of the Literature 
Ligamentum flavum hematoma is a rare condition. Twenty cases including present case have been reported in English-language literature. Among them, only one case reported in pure thoracic spine. A 72-year-old man presented with thoracic myelopathy without precedent cause. Magnetic resonance images revealed a posterior semicircular mass which was located in T7 and T8 level compressing the spinal cord dorsally. T7-8 total laminectomy and extirpation of the mass was performed. One month later following surgery, the patient fully recovered to normal state. Pathologic result was confirmed as ligamentum flavum hematoma. Ligamentum flavum hematoma of rigid thoracic spine is a very rare disease entity. Most reported cases were confined to mobile cervical and lumbar spine. Surgeons should be aware that there seems to be another different pathogenesis other than previously reported cases of mobile cervical and lumbar spine.
doi:10.3340/jkns.2008.44.1.47
PMCID: PMC2588285  PMID: 19096657
Ligamentum flavum; Hematoma; Thoracic spine; Myelopathy
16.  Reversible Plasticity of Fear Memory-Encoding Amygdala Synaptic Circuits Even after Fear Memory Consolidation 
PLoS ONE  2011;6(9):e24260.
It is generally believed that after memory consolidation, memory-encoding synaptic circuits are persistently modified and become less plastic. This, however, may hinder the remaining capacity of information storage in a given neural circuit. Here we consider the hypothesis that memory-encoding synaptic circuits still retain reversible plasticity even after memory consolidation. To test this, we employed a protocol of auditory fear conditioning which recruited the vast majority of the thalamic input synaptic circuit to the lateral amygdala (T-LA synaptic circuit; a storage site for fear memory) with fear conditioning-induced synaptic plasticity. Subsequently the fear memory-encoding synaptic circuits were challenged with fear extinction and re-conditioning to determine whether these circuits exhibit reversible plasticity. We found that fear memory-encoding T-LA synaptic circuit exhibited dynamic efficacy changes in tight correlation with fear memory strength even after fear memory consolidation. Initial conditioning or re-conditioning brought T-LA synaptic circuit near the ceiling of their modification range (occluding LTP and enhancing depotentiation in brain slices prepared from conditioned or re-conditioned rats), while extinction reversed this change (reinstating LTP and occluding depotentiation in brain slices prepared from extinguished rats). Consistently, fear conditioning-induced synaptic potentiation at T-LA synapses was functionally reversed by extinction and reinstated by subsequent re-conditioning. These results suggest reversible plasticity of fear memory-encoding circuits even after fear memory consolidation. This reversible plasticity of memory-encoding synapses may be involved in updating the contents of original memory even after memory consolidation.
doi:10.1371/journal.pone.0024260
PMCID: PMC3176280  PMID: 21949700
17.  Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD 
PLoS Biology  2009;7(9):e1000187.
A two step mechanism was identified that regulates receptor endocytosis during the development of long-term depression (LTD), a long-lasting decrease in synaptic transmission.
Long-term depression (LTD) is a long-lasting activity-dependent decrease in synaptic strength. NMDA receptor (NMDAR)–dependent LTD, an extensively studied form of LTD, involves the endocytosis of AMPA receptors (AMPARs) via protein dephosphorylation, but the underlying mechanism has remained unclear. We show here that a regulated interaction of the endocytic adaptor RalBP1 with two synaptic proteins, the small GTPase RalA and the postsynaptic scaffolding protein PSD-95, controls NMDAR-dependent AMPAR endocytosis during LTD. NMDAR activation stimulates RalA, which binds and translocates widespread RalBP1 to synapses. In addition, NMDAR activation dephosphorylates RalBP1, promoting the interaction of RalBP1 with PSD-95. These two regulated interactions are required for NMDAR-dependent AMPAR endocytosis and LTD and are sufficient to induce AMPAR endocytosis in the absence of NMDAR activation. RalA in the basal state, however, maintains surface AMPARs. We propose that NMDAR activation brings RalBP1 close to PSD-95 to promote the interaction of RalBP1-associated endocytic proteins with PSD-95-associated AMPARs. This suggests that scaffolding proteins at specialized cellular junctions can switch their function from maintenance to endocytosis of interacting membrane proteins in a regulated manner.
Author Summary
Neurons adapt over time in order to dampen their response to prolonged or particularly strong stimuli. This process, termed long-term depression (LTD), results in a long-lasting decrease in the efficiency of synaptic transmission. One extensively studied form of LTD requires the activation of a specific class of receptors known as NMDA glutamate receptors (NMDARs). A key molecular event initiated by NMDA receptor activation is the stimulation of protein phosphatases. Another key event is internalization via endocytosis of synaptic AMPA glutamate receptors (AMPARs). However, the mechanism by which protein dephosphorylation is coupled to AMPAR endocytosis has remained unclear. Here, we help to define this mechanism. We show that endocytic proteins, including RalBP1, are widely distributed in neurons under normal conditions. Upon NMDAR activation, the small GTPase RalA becomes activated and binds to RalBP1, resulting in the translocation of RalBP1 and RalBP1-associated endocytic proteins to synapses. At the same time, RalBP1 becomes dephosphorylated, which promotes its binding to the postsynaptic scaffold protein PSD-95, a protein that itself associates with AMPARs. This concerted recruitment of endocytic proteins to the vicinity of AMPARs results in AMPAR endocytosis. On the basis of our data, we propose a model in which dual binding of RalBP1 to both RalA and PSD-95 following RalBP1 dephosphorylation is essential for NMDAR-dependent AMPAR endocytosis during LTD.
doi:10.1371/journal.pbio.1000187
PMCID: PMC2730530  PMID: 19823667

Results 1-17 (17)