A5035691434- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Genetics and Neurodevelopmental Disorders
- Cholinesterase and Neurodegenerative Diseases
- S100 Proteins and Annexins
- Axon Guidance and Neuronal Signaling
- Receptor Mechanisms and Signaling
- Protein Structure and Dynamics
- Neurogenesis and neuroplasticity mechanisms
- Endoplasmic Reticulum Stress and Disease
- Computational Drug Discovery Methods
- Nicotinic Acetylcholine Receptors Study
- Autism Spectrum Disorder Research
- Signaling Pathways in Disease
- Immune Cell Function and Interaction
- Biotin and Related Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Development and Disorders
- T-cell and B-cell Immunology
- Glycosylation and Glycoproteins Research
- Ion channel regulation and function
- Regulation of Appetite and Obesity
- Tryptophan and brain disorders
- Neurological diseases and metabolism
Rutgers, The State University of New Jersey
2015-2024
Victoria University of Wellington
2019-2024
Université Libre de Bruxelles
2022
Child Health and Development Institute
2012-2020
Johnson University
2012-2019
VIB-KU Leuven Center for Microbiology
2017
Rutgers Sexual and Reproductive Health and Rights
2016
University of Montana
2007-2012
University of California, San Diego
2004-2012
Robert Bosch (India)
2012
A physiological function for sAPP? Although the pathological role of amyloid-β precursor protein (APP) in Alzheimer's disease is well studied, this has remained elusive. Rice et al. found that secreted ectodomain APP (sAPP) binds to GABA B R1a, metabotropic receptor inhibitory neurotransmitter γ-aminobutyric acid (GABA) (see Perspective by Korte). Binding suppressed synaptic vesicle release and modulated transmission plasticity mice. short, 17–amino peptide bound R1a's sushi 1 domain,...
The neuroligins are a family of postsynaptic transmembrane proteins that associate with presynaptic partners, the beta-neurexins. Neurexins and play critical role in initiating formation differentiation synaptic junctions. A recent study reported mutation neuroligin-3 (NL3), an X-linked gene, was found siblings autistic spectrum disorder which two affected brothers had point substituted Cys for Arg451. To characterize at biochemical level, we analyzed expression activity mutated protein....
To study synapse formation by neuroligins, we co-cultured hippocampal neurons with COS cells expressing wild type and mutant neuroligins. The large size of makes it possible to test the effect neuroligins presented over an extended surface area. We found that a uniform lawn displayed on cell triggers hundreds uniformly sized, individual synaptic contacts are labeled neurexin antibodies. Electron microscopy revealed these artificial synapses contain presynaptic active zone docked vesicles...
Latrophilin adhesion-GPCRs (Lphn1-3 or ADGRL1-3) and Unc5 cell guidance receptors (Unc5A-D) interact with FLRT proteins (FLRT1-3), thereby promoting adhesion repulsion, respectively. How the three function simultaneously is poorly understood. We show that Unc5D interacts FLRT2 in cis, controlling response to externally presented Lphn3. The ectodomains of bind cooperatively. Crystal structures ternary complex formed by extracellular domains reveal Lphn3 dimerizes when bound FLRT2:Unc5,...
Protective immune responses against respiratory pathogens, such as severe acute syndrome coronavirus 2 (SARS-CoV-2) and influenza virus, are initiated by the mucosal system. However, most licensed vaccines administered parenterally largely ineffective at inducing immunity. The development of safe effective has been hampered lack a suitable adjuvant. In this study we explore class adjuvant that harnesses mucosal-associated invariant T (MAIT) cells. We show evidence intranasal immunization...
Neuroligins 1-4 are postsynaptic transmembrane proteins capable of initiating presynaptic maturation via interactions with beta-neurexin. Both neuroligins and beta-neurexins have alternatively spliced inserts in their extracellular domains. Using analytical ultracentrifugation, we determined that the domains sediment as dimers, whereas appear monomeric. Sedimentation velocity experiments titrated stoichiometry ratios beta-neurexin neuroligin suggested a 2:2 complex formation. The recognition...
Latrophilins (LPHNs) are a small family of neuronal adhesion-GPCRs originally discovered as receptors for the black widow spider toxin α-latrotoxin. Mutations in LPHN3 have recently been identified risk factors attention deficit hyperactivity disorder (ADHD) humans, but their physiological function has remained elusive. In this study, we tested two hypotheses regarding function: (1) regulates synaptic transmission by modulating probability release; and (2) controls synapse development...
Excitatory and inhibitory neurons are connected into microcircuits that generate circuit output. Central in the hippocampal CA3 microcircuit is mossy fiber (MF) synapse, which provides powerful direct excitatory input indirect feedforward inhibition to pyramidal neurons. Here, we dissect its cell-surface protein (CSP) composition discover novel regulators of MF synaptic connectivity. Proteomic profiling isolated synaptosomes uncovers a rich CSP composition, including many CSPs without...
Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. Cancer cells often hijack these mechanisms to disseminate. Here, we reveal crystal structures Uncoordinated-5 receptor D (Unc5D) in complex with morphogen glypican-3 (GPC3), forming an octameric glycoprotein complex. In complex, four Unc5D molecules pack into antiparallel bundle, flanked by GPC3 molecules. Central glycan-glycan are formed N-linked glycans emanating...
The enhanced cognitive abilities characterizing the human species result from specialized features of neurons and circuits. Here, we report that hominid-specific gene LRRC37B encodes a receptor expressed in cortical pyramidal (CPNs) selectively localized to axon initial segment (AIS), subcellular compartment triggering action potentials. Ectopic expression mouse CPNs vivo leads reduced intrinsic excitability, distinctive feature some classes CPNs. Molecularly, binds secreted ligand FGF13A...
Emerging SARS-CoV-2 variants pose a threat to human health worldwide. receptor binding domain (RBD)-based vaccines are suitable candidates for booster vaccines, eliciting focused antibody response enriched virus neutralizing activity. Although RBD proteins manufactured easily, and have excellent stability safety properties, they poorly immunogenic compared the full-length spike protein. We overcome this limitation by engineering subunit vaccine composed of an tandem dimer fused N-terminal...
Neuroligins, proteins of the α/β-hydrolase fold family, are found as postsynaptic transmembrane whose extracellular domain associates with presynaptic partners, neurexin family. To characterize molecular basis neuroligin interaction neurexin-β, we expressed five soluble and exportable forms neuroligin-1 from recombinant DNA sources, by truncating protein before span near its carboxyl terminus. The functional a dimer when analyzed sedimentation equilibrium. By surface plasmon resonance,...
The composition of the beta-cell exocytic machinery is very similar to that neuronal synapses, and developmental pathway beta-cells neurons substantially overlap. beta-Cells secrete gamma-aminobutyric acid express proteins that, in brain, are specific markers inhibitory synapses. Recently, coculture experiments have identified three families synaptic cell-surface molecules (neurexins, neuroligins, SynCAM) drive synapse formation vitro control differentiation nascent synapses into either...
Although genetic variations in several genes encoding for synaptic adhesion proteins have been found to be associated with autism spectrum disorders, one of the most consistently replicated has CNTNAP2, contactin-associated protein-like 2 (CASPR2), a multidomain transmembrane protein neurexin superfamily. Using immunofluorescence confocal microscopy and complementary biochemical techniques, we compared wild-type CASPR2 12 point mutations identified individuals autism. In contrast protein,...