A5075390520- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- Protist diversity and phylogeny
- Cellular Mechanics and Interactions
- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Photosynthetic Processes and Mechanisms
- Micro and Nano Robotics
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Neurogenetic and Muscular Disorders Research
- Neurogenesis and neuroplasticity mechanisms
- Ubiquitin and proteasome pathways
- RNA regulation and disease
- Photoreceptor and optogenetics research
- Nerve injury and regeneration
- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- Erythrocyte Function and Pathophysiology
- Adenosine and Purinergic Signaling
- ATP Synthase and ATPases Research
University of Pennsylvania
2016-2025
Research Network (United States)
2021-2025
Aligning Science Across Parkinson's
2021-2023
Czech Academy of Sciences, Institute of Physiology
2023
California University of Pennsylvania
2015-2023
History of Science Society
2022
Pennsylvania State University
1983-2017
University of Massachusetts Chan Medical School
2017
Philadelphia University
2012-2015
Wellcome Sanger Institute
2010
Dynein and kinesin motor proteins transport cellular cargoes toward opposite ends of microtubule tracks. In neurons, microtubules are abundantly decorated with microtubule-associated (MAPs) such as tau. Motor thus encounter MAPs frequently along their path. To determine the effects tau on dynein motility, we conducted single-molecule studies moving tau-decorated microtubules. tended to reverse direction, whereas detach at patches bound Kinesin was inhibited about a tenth concentration that...
Mitophagy is a cellular quality control pathway in which the E3 ubiquitin ligase parkin targets damaged mitochondria for degradation by autophagosomes. We examined role of optineurin mitophagy, as mutations are causative amyotrophic lateral sclerosis (ALS) and glaucoma, diseases mitochondrial dysfunction has been implicated. Using live cell imaging, we demonstrate parkin-dependent recruitment to depolarization or reactive oxygen species. Parkin's activity required ubiquitinate outer membrane...
Autophagy is an essential cellular degradation pathway in neurons; defects autophagy are sufficient to induce neurodegeneration. In this paper, we investigate autophagosome dynamics primary dorsal root ganglion neurons. Autophagosome biogenesis occurs distally a constitutive process at the neurite tip. Autophagosomes initially move bidirectionally and then switch unidirectional, processive movement toward cell soma driven by dynein. copurify with anterograde retrograde motors, suggesting...
Autophagy is an essential cellular pathway for degrading defective organelles and aggregated proteins. Defects in autophagy have been implicated the neurodegenerative disorder Huntington's disease (HD), which polyglutamine-expanded huntingtin (polyQ-htt) predominantly cleared by autophagy. In neurons, autophagosomes form constitutively at axon tip undergo robust retrograde axonal transport toward cell body, but factors regulating autophagosome dynamics maturation are not well understood....
Mitochondria play an essential role in maintaining cellular homeostasis. The removal of damaged or depolarized mitochondria occurs via mitophagy, which are targeted for degradation ubiquitination induced by PTEN-induced putative kinase 1 (PINK1) and Parkin. Mitophagy receptors, including optineurin (OPTN), nuclear dot 52 kDa protein (NDP52), Tax1-binding (TAX1BP1), recruited to ubiquitin binding mediate autophagic engulfment through their association with microtubule-associated light chain 3...
Autophagy is an essential degradative pathway that maintains neuronal homeostasis and prevents axon degeneration. Initial observations suggest autophagy spatially regulated in neurons, but how distinct compartments unclear. Using live-cell imaging mouse hippocampal we establish the compartment-specific mechanisms of constitutive under basal conditions, as well response to stress induced by nutrient deprivation. We find at steady state, cell soma contains populations autophagosomes derived...
Regulation of the opposing kinesin and dynein motors that drive axonal transport is essential to maintain neuronal homeostasis. Here, we examine coordination motor activity by scaffolding protein JNK-interacting 1 (JIP1), which find required for long-range anterograde retrograde amyloid precursor (APP) motility in axons. We identify novel interactions between JIP1 heavy chain (KHC) relieve KHC autoinhibition, activating function single molecule assays. The direct binding dynactin subunit...
Ribonucleoprotein (RNP) granules are enriched in specific RNAs and RNA-binding proteins (RBPs) mediate critical cellular processes. Purified RBPs form liquid droplets vitro through liquid-liquid phase separation liquid-like non-membrane-bound structures cells. Mutations the human TAR-DNA binding protein 43 (TDP-43) FUS cause amyotrophic lateral sclerosis (ALS), but biophysical properties of these have not yet been studied neurons. Here, we show that TDP-43 RNP axons rodent primary cortical...
Abstract Mitochondria form interconnected networks that dynamically remodel in response to cellular needs. Using live-cell imaging, we investigate the role of actin cytoskeleton regulating mitochondrial fission and fusion. We identify cycling filaments onto off subsets mitochondria. The association with subpopulations is transient; quickly disassembles, then reassembles around a distinct subpopulation, efficiently through all mitochondria within 14 min. focal assembly induces local,...
Motor-cargo recruitment to microtubules is often the rate-limiting step of intracellular transport, and defects in this can cause neurodegenerative disease. Here, we use vitro reconstitution assays with single-molecule resolution, live-cell transport primary neurons, computational image analysis, computer simulations investigate factors regulating retrograde initiation distal axon. We find that phosphorylation cytoskeletal-organelle linker protein CLIP-170 post-translational modifications...