A5036708034- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Cellular transport and secretion
- Ion channel regulation and function
- Cellular Mechanics and Interactions
- Lipid Membrane Structure and Behavior
- Erythrocyte Function and Pathophysiology
- RNA Research and Splicing
- Axon Guidance and Neuronal Signaling
- Receptor Mechanisms and Signaling
- Microtubule and mitosis dynamics
- Alzheimer's disease research and treatments
- Pluripotent Stem Cells Research
- Adipose Tissue and Metabolism
- Signaling Pathways in Disease
- Nerve injury and regeneration
- 3D Printing in Biomedical Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Pancreatic function and diabetes
- Prion Diseases and Protein Misfolding
- RNA regulation and disease
- MicroRNA in disease regulation
- Nuclear Receptors and Signaling
- Retinal Development and Disorders
- Ubiquitin and proteasome pathways
UNSW Sydney
2014-2024
Universität Hamburg
2006-2016
University Medical Center Hamburg-Eppendorf
2009-2016
Migration Institute of Australia
2015
Martini-Klinik
2010-2012
Oles Honchar Dnipro National University
1998-2001
In spite of advances in understanding the role cellular prion protein (PrP) neural cell interactions, mechanisms PrP function remain poorly characterized. We show that interacts directly with adhesion molecule (NCAM) and associates NCAM at neuronal surface. Both cis trans interactions between surface promote recruitment to lipid rafts thereby regulate activation fyn kinase, an enzyme involved NCAM-mediated signaling. Cis neurite outgrowth. When these are disrupted NCAM-deficient...
The neural cell adhesion molecule (NCAM) has been reported to stimulate neuritogenesis either via nonreceptor tyrosine kinases or fibroblast growth factor (FGF) receptor. Here we show that lipid raft association of NCAM is crucial for activation the kinase pathway and induction neurite outgrowth. Transfection hippocampal neurons NCAM-deficient mice revealed three major isoforms only NCAM140 can act as a homophilic receptor induces Disruption by mutation palmitoylation sites destruction...
Expression of the neural cell adhesion molecule (NCAM) has been shown to promote long-term potentiation (LTP) and stabilization synapses during early synaptogenesis. Here, we searched for mechanisms synaptogenic activity NCAM, focusing on role polysialic acid (PSA), an unusual carbohydrate preferentially associated with NCAM. We show that enzymatic removal PSA endoneuraminidase-N (endo-N) abolished preferential formation NCAM-expressing cells in heterogenotypic cocultures wild-type...
Transformation of a contact between axon and dendrite into synapse is accompanied by accumulation the synaptic machinery at this site, being delivered in intracellular organelles mainly TGN origin. Here, we report that cultured hippocampal neurons, are linked via spectrin to clusters neural cell adhesion molecule (NCAM) plasma membrane. These complexes translocated along neurites trapped sites initial neurite-to-neurite contacts within several minutes after formation. The with NCAM-deficient...
In hippocampal neurons and transfected CHO cells, neural cell adhesion molecule (NCAM) 120, NCAM140, NCAM180 form Triton X-100–insoluble complexes with βI spectrin. Heteromeric spectrin (αIβI) binds to the intracellular domain of NCAM180, isolated subunits bind both as does fragment encompassing second third repeats (βI2–3). NCAM120-transfected is detectable predominantly in lipid rafts. Treatment cells methyl-β-cyclodextrin disrupts NCAM120–spectrin complex, implicating rafts a platform...
The neural cell adhesion molecule (NCAM) forms a complex with p59fyn kinase and activates it via mechanism that has remained unknown. We show the NCAM140 isoform directly interacts intracellular domain of receptor-like protein tyrosine phosphatase RPTPα, known activator p59fyn. Whereas this direct interaction is Ca2+ independent, formation enhanced by Ca2+-dependent spectrin cytoskeleton–mediated cross-linking NCAM RPTPα in response to activation accompanied redistribution lipid rafts....
The neural cell adhesion molecule (NCAM) regulates synapse formation and synaptic strength via mechanisms that have remained unknown. We show NCAM associates with the postsynaptic spectrin-based scaffold, cross-linking N-methyl-d-aspartate (NMDA) receptor Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIalpha) in a manner not firmly or directly linked to PSD95 alpha-actinin. Clustering of promotes detergent-insoluble complexes enriched proteins resembling densities. Disruption...
The Ig superfamily adhesion molecule CHL1, the close homolog of L1, promotes neurite outgrowth, neuronal migration, and survival in vitro . We tested whether similar to its has a beneficial impact on recovery from spinal cord injury using adult CHL1-deficient ( CHL1 −/− ) mice wild-type +/+ littermates. In contrast our hypothesis, we found that functional recovery, assessed by locomotor rating video-based motion analyses, was improved compared with at 3–6 weeks after compression thoracic...
Alzheimer's disease (AD) is characterized by synapse loss due to mechanisms that remain poorly understood. We show the neural cell adhesion molecule 2 (NCAM2) enriched in synapses human hippocampus. This enrichment abolished hippocampus of AD patients and brains mice overexpressing amyloid-β (Aβ) precursor protein carrying pathogenic Swedish mutation. Aβ binds NCAM2 at surface cultured hippocampal neurons induces removal from synapses. In hippocampus, cleavage membrane proximal external...
Changes in expression of the neural cell adhesion molecule 2 (NCAM2) have been proposed to contribute neurodevelopmental disorders humans. The role NCAM2 neuronal differentiation remains, however, poorly understood. Using genetically encoded Ca 2+ reporters, we show that clustering at surface mouse cortical neurons induces submembrane [Ca ] spikes, which depend on L-type voltage-dependent channels (VDCCs) and require activation protein tyrosine kinase c-Src. We also demonstrate VDCC-...
Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM normal mesothelium samples order to identify dysregulated microRNAs with functional roles mesothelioma. We interrogated significant collection tumors our biobank search for novel therapeutic targets. Utilizing mRNA-microRNA correlations based on...
Mice deficient in the neural cell adhesion molecule (NCAM) exhibit increased anxiety and anxiolytic sensitivity to serotonin 5-HT<sub>1A</sub> receptor agonists. Here, we investigate relationship between NCAM signaling pathways modulating G-protein-activated inwardly rectifying K<sup>+</sup> (Kir3) channels. When studying this cultured hippocampal neurons, observed that cells from NCAM-deficient mice, currents were compared with wild-type controls. Analysis of modulatory mechanism...
Changes in neuronal morphology underlying differentiation depend on rapid and sustained cytoskeleton rearrangements the growing neurites. Whereas cell adhesion molecules are well established as regulators of differentiation, less is known about signaling mechanisms by which they influence cytoskeleton. Here we show that neural molecule (NCAM) associates with active form caspase-8 clustering NCAM at surface leads to activation -3 followed cleavage sub-membranous brain spectrin meshwork, but...
Proteins constituting the presynaptic machinery of vesicle release undergo substantial conformational changes during process exocytosis. While in conformation make proteins vulnerable to aggregation and degradation, little is known about synaptic chaperones which counteract these processes. We show that cell adhesion molecule CHL1 directly interacts with regulates activity Hsc70, CSP αSGT. CHL1, αSGT form predominantly CHL1/Hsc70/αSGT CHL1/CSP complexes synapses. Among various formed by...
Newly formed synapses undergo maturation during ontogenetic development via mechanisms that remain poorly understood. We show of the presynaptic endocytotic machinery in CNS neurons requires substitution adaptor protein 3 (AP-3) with AP-2 at plasma membrane. In mature synapses, associates intracellular domain neural cell adhesion molecule (NCAM). NCAM promotes binding over AP-3 to membranes, thus favoring for formation synapses. The remains immature adult NCAM-deficient ( −/−) mice...
In humans, deletions/mutations in the CHL1/CALL gene are associated with mental retardation and schizophrenia. Juvenile CHL1-deficient (CHL1(-/-) ) mice have been shown to display abnormally high numbers of parvalbumin-expressing (PV(+) hippocampal interneurons and, as adults, behavioral traits observed neuropsychiatric disorders. Here, we addressed question whether inhibitory synaptic plasticity CHL1(-/-) mouse affected during brain maturation adulthood. We found that hippocampal, but not...
Extension of axonal and dendritic processes in the CNS is tightly regulated by outgrowth-promoting -inhibitory cues to assure precision synaptic connections. We identify a novel role for contactin-associated protein (Caspr) as an inhibitory cue that reduces neurite outgrowth from neurons. show proteolysis Caspr at cell surface cellular form prion (PrP), which directly binds Caspr. PrP inhibits Reelin-mediated shedding surface, thereby increasing levels potentiating effect on outgrowth....