A5054228916- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Alzheimer's disease research and treatments
- Autophagy in Disease and Therapy
- Photoreceptor and optogenetics research
- Retinal Development and Disorders
- Stress Responses and Cortisol
- Endoplasmic Reticulum Stress and Disease
- Tryptophan and brain disorders
- Calcium signaling and nucleotide metabolism
- S100 Proteins and Annexins
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion channel regulation and function
- Parkinson's Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Microtubule and mitosis dynamics
- Extracellular vesicles in disease
- MicroRNA in disease regulation
- Neuroscience and Neural Engineering
- Advanced Fluorescence Microscopy Techniques
- Nitric Oxide and Endothelin Effects
- Reproductive System and Pregnancy
- Polyamine Metabolism and Applications
- Axon Guidance and Neuronal Signaling
Columbia University Irving Medical Center
2016-2025
Columbia University
2015-2025
New York Proton Center
2025
Stanford University
2005-2017
Palo Alto University
2005-2016
Institute of Cell Biology
2016
University of California, San Francisco
1998-2005
Active zones are specialized regions of the presynaptic plasma membrane designed for efficient and repetitive release neurotransmitter via synaptic vesicle (SV) exocytosis. Piccolo is a high molecular weight component active zone that hypothesized to participate both in formation scaffolding key molecules involved SV recycling. In this study, we use interference RNAs eliminate expression from cultured hippocampal neurons assess its involvement synapse function. Our data show not required...
Synaptic vesicle (SV) pools must maintain a functional repertoire of proteins to efficiently release neurotransmitter. The accumulation old or damaged on SV membranes is linked synaptic dysfunction and neurodegeneration. However, despite the importance protein turnover for neuronal health, molecular mechanisms underlying this process are largely unknown. Here, we have used dissociated rat hippocampal neurons investigate pathway degradation. We find that activity drives degradation subset...
Abstract Prolonged exposure to glucocorticoids, the main stress hormones, damages brain and is a risk factor for depression Alzheimer's disease. Two major drivers of glucocorticoid-related neurotoxicity are mitochondrial dysfunction Tau pathology; however, molecular/cellular mechanisms precipitating these events, their causal relationship, remain unclear. Using cultured murine hippocampal neurons 4–5-month-old mice treated with synthetic glucocorticoid dexamethasone, we investigate...
The synaptic insertion of GluR1-containing AMPA-type glutamate receptors (AMPARs) is critical for plasticity. However, mechanisms responsible GluR1 and retention at the synapse are unclear. synapse-associated protein SAP97 directly binds participates in its forward trafficking from Golgi network to plasma membrane. Whether also plays a role scaffolding postsynaptic membrane controversial, attributable expression as collection alternatively spliced isoforms with ill-defined spatial temporal...
Filamentous (F)-actin is a known regulator of the synaptic vesicle (SV) cycle, with roles in SV mobilization, fusion, and endocytosis. However, molecular pathways that regulate its dynamic assembly within presynaptic boutons remain unclear. In this study, we have used shRNA-mediated knockdown to demonstrate Piccolo, multidomain protein active zone cytomatrix, key F-actin assembly. Boutons lacking Piccolo exhibit enhanced activity-dependent Synapsin1a dispersion exocytosis, reduced...
Extracellular vesicles (EVs), including small EVs (sEVs) such as exosomes, exhibit great potential for the diagnosis and treatment of brain disorders, representing a valuable tool precision medicine. The latter demands high-quality human biospecimens, especially in complex disorders which pathological specimen heterogeneity, well diverse individual clinical profile, often complicate development therapeutic schemes patient-tailored treatments. Thus, collection characterization physiologically...
Specific transport proteins mediate the packaging of neurotransmitters into secretory vesicles and consequently require targeting to appropriate intracellular compartment. To identify residues in neuron-specific vesicular monoamine transporter (VMAT2) responsible for endocytosis, we examined effect amino (NH2-) carboxyl (COOH-)-terminal mutations on steady state distribution internalization. Deletion a critical COOH-terminal domain sequence (AKEEKMAIL) results accumulation VMAT2 at plasma...
Vesicular transport proteins package classical neurotransmitters for regulated exocytotic release, and localize to at least two distinct types of secretory vesicles. In PC12 cells, the vesicular acetylcholine transporter (VAChT) localizes preferentially synaptic-like microvesicles (SLMVs), whereas closely related monoamine transporters (VMATs) large dense core vesicles (LDCVs). VAChT VMATs contain COOH-terminal, cytoplasmic dileucine motifs required internalization from plasma membrane. We...
The dynamic assembly of filamentous (F) actin plays essential roles in the presynaptic boutons, fusion, mobilization and recycling synaptic vesicles (SVs), forms plasticity. However, molecular mechanisms that regulate temporal spatial F-actin remain largely unknown. Similar to other rich membrane specializations, boutons contain a set molecules respond cellular cues trans-synaptic signals facilitate activity-dependent F-actin. active zone (AZ) protein Piccolo has recently been identified as...
The release of biogenic amines from large dense core vesicles (LDCVs) depends on localization the vesicular monoamine transporter VMAT2 to LDCVs. We now find that a cluster acidic residues including two serines phosphorylated by casein kinase 2 is required for Deletion promotes removal LDCVs during their maturation. motif thus acts as signal retention In addition, replacement glutamate mimic phosphorylation LDCVs, whereas alanine prevent decreases removal. Phosphorylation appears reduce...