A5081952594- Genetics, Aging, and Longevity in Model Organisms
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Neurobiology and Insect Physiology Research
- Microtubule and mitosis dynamics
- Endoplasmic Reticulum Stress and Disease
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Mitochondrial Function and Pathology
- Axon Guidance and Neuronal Signaling
- Retinal Development and Disorders
- Signaling Pathways in Disease
- Genetics and Neurodevelopmental Disorders
- Autophagy in Disease and Therapy
Florida Institute of Technology
2023-2024
Scripps Research Institute
2016-2019
Florida Atlantic University
2014-2017
Abstract Autophagy is an intracellular catabolic process prominent in starvation, aging and disease. Neuronal autophagy particularly important, as it affects the development function of nervous system, heavily implicated neurodegenerative Nonetheless, how regulated neurons remains poorly understood. Using unbiased proteomics approach, we demonstrate that primary initiator autophagy, UNC-51/ULK kinase, negatively by ubiquitin ligase RPM-1. RPM-1 activity restricts UNC-51 autophagosome...
Axon termination is essential for efficient and accurate nervous system construction. At present, relatively little known about how growth cone collapse occurs prior to axon in vivo. Using the mechanosensory neurons of C. elegans, we found protracted, with transitioning from a dynamic static state. Growth facilitated by signaling hub RPM-1. Given prominence cytoskeleton collapse, assessed relationship between RPM-1 regulators actin dynamics microtubule stability. Our results reveal several...
The ubiquitin ligase Highwire has a conserved role in synapse formation. Here, we show that coordinates several facets of central formation the Drosophila melanogaster giant fiber system, including axon termination, pruning, and synaptic function. Despite similarities to fly neuromuscular junction, underlying signaling pathways are distinct fly's system. During development, branching presynaptic terminal occurs and, normally, transient branches pruned away. However, highwire mutants these...
Netrin and its receptor, Frazzled, dictate the strength of synaptic connections in giant fiber system (GFS) Drosophila melanogaster by regulating gap junction localization presynaptic terminal. In mutant animals, coupling between a interneuron “jump” motor neuron was weakened dye these two neurons severely compromised or absent. cases which mutants displayed apparently normal anatomy, half specimens exhibited physiologically defective synapses (GF) reduced eliminated, suggesting that...
Synapse formation is comprised of target cell recognition, synapse assembly, and maintenance. Maintaining established synaptic connections essential for generating functional circuitry instability a hallmark neurodegenerative disease. While many molecules impact generally, we know little about that affect maintenance in vivo. Using genetics developmental time course analysis C.elegans, show the α-tubulin acetyltransferase ATAT-2 signaling hub RPM-1 are required presynaptically to maintain...
ABSTRACT Alzheimer's disease is associated with the misfolding and aggregation of two distinct proteins, beta-amyloid tau. Previously, it has been shown that activation cytoprotective heat shock response (HSR) pathway reduces toxicity. Here, we show HSR also protective against tau toxicity in a cell-autonomous manner. Overexpression HSF-1, master regulator HSR, ameliorates motility defect increases lifespan transgenic C. elegans expressing human By contrast, RNA interference HSF-1...
Abstract Ubiquitin ligases are important regulators of nervous system development, function and disease. To date, numerous ubiquitin have been discovered that regulate presynaptic biology. Here, we discuss recent findings on include members from the three major ligase classes: RING, RBR HECT. Several themes emerge based across a range model systems. A cadre is required presynaptically to orchestrate development transmission at synapses. Multiple deploy both enzymatic non‐enzymatic...
Integrin signaling plays important roles in development and disease. An adhesion network called the integrin adhesome has been principally defined using bioinformatics cell-based proteomics. To date, not studied integrated proteomic genetic approaches. Here, studies C . elegans identified physical associations between RPM-1 ubiquitin ligase hub numerous components including Talin (TLN-1), Kindlin (UNC-112) β-integrin (PAT-3). is orthologous to human MYCBP2, a prominent player nervous system...
Integrin signaling plays important roles in development and disease. An adhesion network called the integrin adhesome has been principally defined using bioinformatics proteomics. To date, not studied integrated proteomic genetic approaches. Here, studies