A5024320075- Phosphodiesterase function and regulation
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Tryptophan and brain disorders
- Autophagy in Disease and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Axon Guidance and Neuronal Signaling
- Cannabis and Cannabinoid Research
- Cholinesterase and Neurodegenerative Diseases
- Renin-Angiotensin System Studies
- Cellular transport and secretion
- Stress Responses and Cortisol
- 14-3-3 protein interactions
- Genetics, Aging, and Longevity in Model Organisms
- Alzheimer's disease research and treatments
- Neurotransmitter Receptor Influence on Behavior
- Nerve injury and regeneration
- Chemical synthesis and alkaloids
- MicroRNA in disease regulation
- Neurobiology and Insect Physiology Research
- Neurogenesis and neuroplasticity mechanisms
- TGF-β signaling in diseases
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Congenital heart defects research
Centre for Addiction and Mental Health
2016-2024
University of Toronto
2016-2024
Mental Health Research Institute
2020-2023
Kyoto University
2014-2022
Beckman Research Institute
2006-2022
City of Hope
2006-2022
Mental Health Research Canada
2020-2021
Kyoto Medical Center
2016-2019
Miyazaki International College
2015
City Of Hope National Medical Center
2007-2009
Disrupted-in-Schizophrenia-1 ( DISC-1 ) is a gene whose mutant truncation associated with major psychiatric illness predominance of schizophrenic symptomatology. We have cloned and characterized rodent DISC-1. expression displays pronounced developmental regulation the highest levels in late embryonic life when cerebral cortex develops. In yeast two-hybrid analyses, interacts variety cytoskeletal proteins. One these, NudE-like (NUDEL), cortical development linked to LIS-1, disease for form...
Previous studies showed that the serine/threonine kinase Unc51.1 is one of earliest genes in neuronal differentiation and required for granule cell axon formation. To examine mechanism regulation extension, we have identified two direct binding partners. The first, SynGAP, a negative regulator Ras, expressed within axons growth cones developing cells. Overexpression SynGAP blocks neurite outgrowth by involves Ras-like GTPase cascade. second partner PDZ domain-containing scaffolding protein,...
Disrupted-In-Schizophrenia-1 (DISC1) is a unique susceptibility gene for major mental conditions, because of the segregation its genetic variant with hereditary psychosis in Scottish pedigree. Genetic association studies reproducibly suggest involvement DISC1 both schizophrenia and bipolar disorder several ethnic groups. The protein multifunctional, pool dynein motor complex required neurite outgrowth PC12 cells as well proper neuronal migration dendritic arborization developing cerebral...
The cortical regions of the brain are laminated as a result directed migration precursor cells along glia during development. Previously, we have used an assay system to identify astrotactin neuronal ligand for on glial fibers. To examine function in vivo, generated null mutation by targeted gene disruption. cerebella mice approximately 10% smaller than wild type. In vitro and vivo cerebellar granule cell assays show decrease neuron-glial binding, reduction rates abnormal development...
Axonal transport mediated by microtubule-dependent motors is vital for neuronal function and viability. Selective sets of cargoes, including macromolecules organelles, are transported long range along axons to specific destinations. Despite intensive studies focusing on the motor machinery, regulatory mechanisms that control motor–cargo assembly not well understood. Here we show UNC-51/ATG1 kinase regulates interaction between synaptic vesicles complexes during in Drosophila . UNC-51 binds...
The molecular mechanism and significance of endocytic processes involved in directional axon elongation are not well understood. Unc-51 family serine/threonine kinases was shown to be important for growth also linked endocytosis, providing an entry point study this problem. We found that mouse Unc-51-like kinase 1/2 (Ulk1/2) proteins localized vesicular structures cones spinal sensory neurons. RNAi-mediated knockdown Ulk1 and/or Ulk2 resulted impaired endocytosis nerve factor (NGF),...
Neuregulin-1 (NRG1) and its receptor ErbB4 influence several processes of neurodevelopment, but the mechanisms regulating this signalling in mature brain are not well known. DISC1 is a multifunctional scaffold protein that mediates many cellular processes. Here we present functional relationship between NRG1-ErbB4 cortical interneurons. By cell type-specific gene modulation vitro vivo including mutant mouse model, demonstrate inhibits NRG1-induced activation signalling. This effect likely...
Efficient synaptic transmission requires the apposition of neurotransmitter release sites opposite clusters postsynaptic receptors. Transmitter is released at active zones, which are composed a large complex proteins necessary for development and function. Many zone have been identified, but little known mechanisms that ensure each receives proper complement proteins. Here we use genetic analysis in Drosophila to demonstrate serine threonine kinase Unc-51 acts presynaptic motoneuron regulate...
In the developing cerebellum, granule neuron axon outgrowth is a key step toward establishing proper connections with Purkinje neurons, principal output of cerebellum. During search for genes that function in this process, we identified receptor tyrosine kinase discoidin domain 1 (DDR1) expressed cells throughout their development. Overexpression dominant-negative form DDR1 immature results severe reduction neurite vitro, dissociated primary culture, and vivo, organotypic slices neonatal...
Autophagy plays an essential role in intracellular degradation and maintenance of cellular homeostasis all cells, including neurons. Although a recent study reported copy number variation Ulk2, gene for initiating autophagy, associated with case schizophrenia (SZ), it remains to be studied whether Ulk2 dysfunction could underlie the pathophysiology disease. Here we show that heterozygous (Ulk2+/-) mice have upregulated expression sequestosome-1/p62, autophagy-associated stress response...
22q11.2 deletions, a genetic risk for schizophrenia, could be susceptible to Parkinson’s disease through elevated expression of α-synuclein.
Background Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for protein, including axonal elongation, growth cone guidance, synaptic vesicle transport. Methodology/Principal Findings In this work, we investigated functional significance Unc-51-mediated transport complex brain structures Drosophila. We show preferentially...