A5022355683- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Autoimmune Neurological Disorders and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Wnt/β-catenin signaling in development and cancer
- Microtubule and mitosis dynamics
- Receptor Mechanisms and Signaling
- Genetics and Neurodevelopmental Disorders
- Hippo pathway signaling and YAP/TAZ
- Endoplasmic Reticulum Stress and Disease
- Cellular Mechanics and Interactions
- Lipid Membrane Structure and Behavior
- Photoreceptor and optogenetics research
- Monoclonal and Polyclonal Antibodies Research
- Skin and Cellular Biology Research
- Peptidase Inhibition and Analysis
- Ion channel regulation and function
- Glycosylation and Glycoproteins Research
- Peripheral Neuropathies and Disorders
- Alzheimer's disease research and treatments
- Neuroscience and Neural Engineering
- Ubiquitin and proteasome pathways
- Pancreatic function and diabetes
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
National Institutes of Natural Sciences
2016-2025
National Institute for Physiological Sciences
2016-2025
Nagoya University
2000-2025
The Graduate University for Advanced Studies, SOKENDAI
2015-2024
Department of Physiological Sciences
2020-2024
Fukuoka International University
2023
International University of Health and Welfare
2023
University of the Ryukyus
2023
Tokyo Women's Medical University Hospital
2023
Kyushu University
2023
The small guanosine triphosphatases (GTPases) Cdc42 and Rac1 regulate E-cadherin-mediated cell-cell adhesion. IQGAP1, a target of Rac1, was localized with E-cadherin beta-catenin at sites contact in mouse L fibroblasts expressing (EL cells), interacted both vivo vitro. IQGAP1 induced the dissociation alpha-catenin from cadherin-catenin complex vitro vivo. Overexpression EL cells, but not cells an E-cadherin-alpha-catenin chimeric protein, resulted decrease adhesive activity. Thus, acting...
Abnormally synchronized synaptic transmission in the brain causes epilepsy. Most inherited forms of epilepsy result from mutations ion channels. However, one form epilepsy, autosomal dominant partial with auditory features (ADPEAF), is characterized by a secreted neuronal protein, LGI1. We show that ADAM22, transmembrane protein when mutated itself seizure, serves as receptor for LGI1 enhances AMPA receptor-mediated hippocampal slices. The fails to bind ADAM22. ADAM22 anchored postsynaptic...
More than 30 mutations in LGI1, a secreted neuronal protein, have been reported with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although LGI1 haploinsufficiency is thought to cause ADLTE, the underlying molecular mechanism that results abnormal brain excitability remains mysterious. Here, we focused on mode of action autoantibodies associated limbic encephalitis (LE), which one acquired epileptic disorders characterized by subacute onset amnesia and seizures. We...
Epilepsy is a devastating and poorly understood disease. Mutations in secreted neuronal protein, leucine-rich glioma inactivated 1 (LGI1), were reported patients with an inherited form of human epilepsy, autosomal dominant partial epilepsy auditory features (ADPEAF). Here, we report essential role LGI1 as antiepileptogenic ligand. We find that loss mice (LGI1(-/-)) causes lethal which specifically rescued by the expression transgene, but not LGI3. Moreover, heterozygous for mutation...
Distinct PSD-95 clusters are primary landmarks of postsynaptic densities (PSDs), which specialized membrane regions for synapses. However, the mechanism that defines locations and whether or how they reorganized inside individual dendritic spines remains controversial. Because palmitoylation regulates targeting, we combined a conformation-specific recombinant antibody against palmitoylated with live-cell super-resolution imaging discovered subsynaptic nanodomains composed serve as elementary...
Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential for its synaptic clustering regulation of AMPA receptor However, molecular mechanisms palmitate cycling remain incompletely understood, as depalmitoylating enzymes unknown. Here, we isolated 38 mouse or rat serine hydrolases found that subset specifically depalmitoylated heterologous cells. These...
Cdc42 and Rac1 have been implicated in the regulation of various cell functions such as morphology, polarity, proliferation. We partially purified a Cdc42- Rac1-associated protein with molecular mass about 170 kDa (p170) from bovine brain cytosol. This interacted guanosine 5′-(3-O-thio)triphosphate (GTPγS)·glutathione S-transferase (GST)-Cdc42 GTPγS·GST-Rac1 but not GDP·GST-Cdc42, GDP·GST-Rac1, or GTPγS·GST-RhoA). identified p170 an IQGAP, which is originally putative Ras GTPase-activating...
ABSTRACT Rac1, a member of the Rho family small GTPases, regulates E-cadherin-mediated cell-cell adhesion. However, it remains to be clarified how localization and activation Rac1 are regulated at sites contact. Here, using enhanced green fluorescence protein (EGFP)-tagged we demonstrate that EGFP-Rac1 is colocalized with E-cadherin contact translocates cytosol during disruption adhesion by Ca2+ chelation. Re-establishment restoration caused become relocalized, together E-cadherin,...
Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival and differentiation during development synaptic function plasticity in the mature brain. BDNF-containing vesicles are widely distributed bidirectionally transported neurons, secreted BDNF can act on both presynaptic postsynaptic cells. Activity-dependent secretion from cultures has been reported, but it remains unknown where primary site of whether activity trigger axons dendrites with equal efficacy. Using fused...
Rac1 small GTPase plays pivotal roles in various cell functions such as morphology, polarity, and proliferation. We have previously identified IQGAP1 from bovine brain cytosol a target for by an affinity purification method. By using the same method, we purified specifically Rac1-associated protein with molecular mass of about 140 kDa (p140) cytosol. This interacted guanosine 5′-(3-<i>O</i>-thio)triphosphate (GTPγS)·glutathione<i>S</i>-transferase (GST)-Rac1 but not GDP·GST-Rac1,...
Activity-dependent plasticity in the brain arises part from changes number of synaptic AMPA receptors. Synaptic trafficking receptors is controlled by stargazin and homologous transmembrane receptor regulatory proteins (TARPs). We found that TARPs were stable at plasma membrane, whereas internalized a glutamate-regulated manner. Interaction with involved both extra- intracellular determinants TARPs. Upon binding to glutamate, detached This did not require ion flux or second messengers....
IQGAP1, a target of Cdc42 and Rac1 small GTPases, directly interacts with β-catenin negatively regulates E-cadherin-mediated cell-cell adhesion by dissociating α-catenin from the cadherin-catenin complex <i>in vivo</i> (Kuroda, S., Fukata, M., Nakagawa, Fujii, K., Nakamura, T., Ookubo, Izawa, I., Nagase, Nomura, N., Tani, H., Shoji, Matsuura, Y., Yonehara, Kaibuchi, K. (1998) <i>Science</i> 281, 832–835). Here we investigated how regulate IQGAP1 function. interacted amino-terminal region...
Protein palmitoylation is the most common posttranslational lipid modification; its reversibility mediates protein shuttling between intracellular compartments. A large family of DHHC (Asp-His-His-Cys) proteins has emerged as palmitoyl acyltransferases (PATs). However, mechanisms that regulate these PATs in a physiological context remain unknown. In this study, we efficiently monitored dynamic palmitate cycling on synaptic scaffold PSD-95. We found blocking activity rapidly induces PSD-95...
We have previously shown that IQGAP1, a recently identified target for Cdc42 and Rac1 small GTPases, showed distribution similar to of cortical actin cytoskeleton at the membrane ruffling area induced by insulin Rac1val12 (Kuroda, S., Fukata, M., Kobayashi, K., Nakafuku, Nomura, N., Iwamatsu, A., Kaibuchi, K. (1996) J. Biol. Chem. 271, 23363–23367). Here we an IQGAP1-interacting molecule with molecular mass 43 kDa (p43) from bovine brain cytosol, using glutathione S-transferase (GST)-IQGAP1...
Golgi-specific DHHC (Asp-His-His-Cys) zinc finger protein (GODZ) is a family palmitoyl acyltransferase that implicated in palmitoylation and regulated trafficking of diverse substrates function either at inhibitory or excitatory synapses. Of particular interest the γ2 subunit GABA A receptors, which required for targeting these receptors to Here, we report GODZ and, lesser extent, its close paralog sertoli cell gene with domain-β (SERZ-β) are main members enzymes able palmitoylate...
Rac1 and Cdc42, members of the Rho family GTPases, control diverse cellular processes such as cell migration morphogenesis through their effectors. Among effectors, IQGAP1 plays pivotal roles in establishment cytoskeletal architecture intercellular adhesions various cells. However, its remain to be clarified, especially neuronal We have identified IQGAP3 a novel member IQGAP family, which is highly expressed brain. found that IQGAP3, an effector associates directly with actin filaments...
Autoimmune forms of encephalitis have been associated with autoantibodies against synaptic cell surface antigens such as NMDA- and AMPA-type glutamate receptors, GABA<sub>B</sub> receptor, LGI1. However, it remains unclear how many autoantigens are yet to be defined. Using immunoproteomics, we identified the GABA<sub>A</sub> receptor in human sera from two patients diagnosed who presented cognitive impairment multifocal brain MRI abnormalities. Both had antibodies directed extracellular...