A5091587199- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Health and Medical Research Impacts
- Protein Kinase Regulation and GTPase Signaling
- Innovations in Medical Education
- Health Sciences Research and Education
- Retinal Development and Disorders
- Ion channel regulation and function
- Photoreceptor and optogenetics research
- Cannabis and Cannabinoid Research
- Phytase and its Applications
- Parkinson's Disease Mechanisms and Treatments
- RNA Interference and Gene Delivery
- ATP Synthase and ATPases Research
- Genetics and Neurodevelopmental Disorders
- Cardiomyopathy and Myosin Studies
- Mitochondrial Function and Pathology
- Neurobiology and Insect Physiology Research
- Lysosomal Storage Disorders Research
- Microtubule and mitosis dynamics
- Advances in Oncology and Radiotherapy
- Alzheimer's disease research and treatments
- Endoplasmic Reticulum Stress and Disease
- Biochemical effects in animals
University of California, San Francisco
2007-2025
Johns Hopkins University
1988-1998
Johns Hopkins Medicine
1988-1996
The presynaptic protein alpha-synuclein has a central role in Parkinson's disease (PD). However, the mechanism by which contributes to neurodegeneration and its normal function remain unknown. Alpha-synuclein localizes nerve terminal interacts with artificial membranes vitro but binds weakly native brain membranes. To characterize membrane association of living neurons, we used fluorescence recovery after photobleaching. Despite enrichment at synapse, is highly mobile, rapid exchange between...
Diphosphoinositol pentakisphosphate (PP-IP5) and bis(diphospho)inositol tetrakisphosphate (bis-PP-IP4) are recently identified inositol phosphates that possess pyrophosphate bonds. We have purified an hexakisphosphate (IP6) kinase from rat brain supernatants. The pure protein, a monomer of 54 kDa, displays high affinity (Km = 0.7 microM) selectivity for as substrate. It can be dissociated synthetic activity. enzyme transfers phosphate PP-IP5 to ADP form ATP. This ATP synthase activity...
To clarify the function of receptor binding protein for inositol hexakisphosphate (IP6), we obtained a partial amino acid sequence from purified and nucleotide cDNA clone gene. The sequences are essentially identical to those α-subunit clathrin assembly AP-2. IP6 analyzed by SDS-PAGE contains series subunits which same as Antibodies AP-2 react with in immunoblot analysis.
Astrocytes are the most abundant glial cell type in brain. Although not apposite for long-range rapid electrical communication, astrocytes share with neurons capacity of chemical signaling via Ca 2+ -dependent transmitter exocytosis. Despite this recent finding, little is known about specific properties regulated secretion and vesicle recycling astrocytes. Important differences may exist neuronal exocytosis, starting from fact that stimulus-secretion coupling voltage independent, mediated by...
Thimerosal, a sulfhydryl oxidizing reagent, has been shown to induce Ca2+ mobilization in several cell types and increase the sensitivity of intracellular stores inositol 1,4,5-trisphosphate (IP3). Using purified IP3 receptor (IP3R) protein reconstituted vesicles, we demonstrate pronounced stimulation by thimerosal its channel activity. Effects are dependent on redox state receptor, implying an action critical group(s) IP3R. Thimerosal enhances affinity IP3R for binding. The manner which...
The vesicular glutamate transporters (VGLUTs) package into synaptic vesicles, and the two principal isoforms VGLUT1 VGLUT2 have been suggested to influence properties of release. To understand how a VGLUT isoform might transmitter release, we studied their trafficking previously identified dileucine-like endocytic motif in C terminus VGLUT1. Disruption this impairs activity-dependent recycling VGLUT1, but does not eliminate its endocytosis. We now report identification additional motifs N...
Increasing evidence indicates that individual synaptic vesicle proteins may use different signals, endocytic adaptors, and trafficking pathways for sorting to distinct pools of vesicles. Here, we report the identification a unique amino acid motif in vesicular GABA transporter (VGAT) controls its localization activity-dependent recycling. Mutational analysis this atypical dileucine-like rat VGAT recycles by interacting with clathrin adaptor protein AP-2. However, mutation single acidic...
Release of the major excitatory neurotransmitter glutamate by synaptic vesicle exocytosis depends on loading into vesicles vesicular transporters (VGLUTs). The two principal isoforms, VGLUT1 and 2, exhibit a complementary pattern expression in adult brain that broadly distinguishes cortical (VGLUT1) subcortical (VGLUT2) systems, correlates with distinct physiological properties synapses expressing these isoforms. Differential trafficking 2 has been suggested to underlie their functional...
Diphosphoinositol pentakisphosphate (PP-IP5) and bis(diphospho)inositol tetrakisphosphate (bis-PP-IP4) were recently identified as inositol phosphates which possess pyrophosphate bonds. The molecular mechanisms that regulate the cellular levels of these compounds are not yet characterized. To pursue this question, we have previously purified an hexakisphosphate (IP6) kinase from rat brain supernatants [Voglmaier, S. M., et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 4305−4310]. We now...
Inositol pyrophosphates have been implicated in cellular signaling and membrane trafficking, including synaptic vesicle (SV) recycling. hexakisphosphate kinases (IP6Ks) their product, diphosphoinositol pentakisphosphate (PP-IP5 or IP7), directly indirectly regulate proteins important recycling by the activity-dependent bulk endocytosis pathway (ADBE). In present study, we show that two isoforms, IP6K1 IP6K3, are expressed axons. The role of SV investigated using pharmacologic inhibition,...
Exocytotic release of glutamate depends upon loading the neurotransmitter into synaptic vesicles by vesicular transporters, VGLUTs. The major isoforms, VGLUT1 and 2, exhibit a complementary pattern expression in synapses adult rodent brain that correlates with probability potential for plasticity. Indeed, different VGLUT protein isoforms confers properties probability. Expression or 2 also determines kinetics vesicle recycling. To identify molecular determinants may be related to reported...
Clinical and genetic features of five unrelated patients with de novo pathogenic variants in the synaptic vesicle-associated membrane protein 2 (VAMP2) reveal common global developmental delay, autistic tendencies, behavioral disturbances, a higher propensity to develop epilepsy. For one patient, cognitively impaired adolescent stop-gain VAMP2 mutation, we tested potential treatment strategy, enhancing neurotransmission by prolonging action potentials aminopyridine family potassium channel...
Abstract: Radioligand binding studies with the water‐soluble cannabinoid [ 3 H]5′‐trimethylammonium A 8 ‐tetrahydrocannabinol ([ H]TMA) have revealed a saturable highaffinity site in brain that is specific for cannabinoids. To determine whether endogenous compounds of might act upon physiologically, we sought inhibitors extracts brain. An inhibitor has been purified to homogeneity by acid extraction rat followed adsorption reverse‐phase matrix and gel filtration chromatography. The subunit...
Dictyostelium discoideum utilizes G-protein-regulated transmembrane signaling systems to implement its developmental program. This report describes the G-protein α-subunit, Gα3, and demonstrates that it is required for normal development. Gα3 largest of four completely sequenced α-subunits. The difference in size due variability N-terminal regions. regions which are affected by increased Gβγ binding region helical domain protects guanine nucleotide cleft. gα3− mutants created gene disruption...
Abstract: The high‐affinity cannabinoid site in rat brain is an integral component of membranes that recognizes cannabinoids with inhibitory constants ( K i ) the nanomolar range. To clarify its physiological role, we studied regulation [ 3 H]5′‐trimethylammonium Δ 8 ‐tetrahydrocannabinol ([ H]TMA) binding. inhibited by heavy metal ions, such as La 3+ , at low micromolar concentrations; divalent cations, Ca 2+ and Mg inhibit H]TMA binding, though somewhat higher concentrations. In contrast,...