A5079250115- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Protist diversity and phylogeny
- Alzheimer's disease research and treatments
- Neurogenesis and neuroplasticity mechanisms
- Axon Guidance and Neuronal Signaling
- 14-3-3 protein interactions
- Photosynthetic Processes and Mechanisms
- Plant Molecular Biology Research
- Mitochondrial Function and Pathology
- Hippo pathway signaling and YAP/TAZ
- ATP Synthase and ATPases Research
- Advanced Fluorescence Microscopy Techniques
- Protein Structure and Dynamics
- Advanced Neuroimaging Techniques and Applications
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Photoreceptor and optogenetics research
- Cardiomyopathy and Myosin Studies
- Genetics and Neurodevelopmental Disorders
- Cancer Treatment and Pharmacology
- Particle Dynamics in Fluid Flows
- Pancreatic function and diabetes
University of California, Davis
2017-2025
University of California System
2022-2025
University of California, Los Angeles
2021-2024
University of California, San Francisco
2012-2022
Howard Hughes Medical Institute
2012-2016
University College London
2012
Columbia University
2010-2012
Cedars-Sinai Medical Center
2012
Wayne State University
2012
MRC Prion Unit
2012
Atrophy of neurons in the prefrontal cortex (PFC) plays a key role pathophysiology depression and related disorders. The ability to promote both structural functional plasticity PFC has been hypothesized underlie fast-acting antidepressant properties dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable robustly increasing neuritogenesis and/or spinogenesis vitro vivo. These changes neuronal structure accompanied by increased synapse...
Within cells, motor and non-motor microtubule-associated proteins (MAPs) simultaneously converge on the microtubule. How binding activities of MAPs are coordinated how they contribute to balance distribution transport is unknown. Here, we examine relationship between MAP7 tau owing their antagonistic roles in vivo. We find that compete for microtubules, determine a mechanism by which displaces from lattice. promotes kinesin-based vivo strongly recruits kinesin-1 microtubule vitro, providing...
To identify the gene responsible for 14q32-linked dominant spinal muscular atrophy with lower extremity predominance (SMA-LED, OMIM 158600).
Both cell-intrinsic and extrinsic pathways govern axon regeneration, but only a limited number of factors have been identified it is not clear to what extent regeneration evolutionarily conserved. Whether dendrites also regenerate unknown. Here we report that, like the axons mammalian sensory neurons, certain Drosophila dendritic arborization (da) neurons are capable substantial in periphery CNS, activating Akt pathway enhances CNS. Moreover, those da display dendrite which cell...
Kinesin-1 activity is regulated by autoinhibition. Intramolecular interactions within the kinesin heavy chain (KHC) are proposed to be one facet of motor regulation. The KHC also binds light (KLC), which has been implicated in both autoinhibition and activation motor. We show that KLC inhibits kinesin-microtubule interaction independently from intramolecular KHC. Cargo-adaptor proteins bind stimulated processive movement, but landing rate activated complexes remained low....
Nesprin-2 Giant (N2G) is a large integral membrane protein that physically connects the nucleus to cytoskeleton, but how N2G performs this activity maintain nuclear positioning and drive movement unclear. This study investigates N2G's role in nucleocytoskeletal coupling, process critical for cellular function development. We uncover multiple roles N2G, including its as an F-actin bundler, adapter activates kinesin-1 motors, mediator of cytoskeletal cross-talk. Notably, directly links...
The specific physiological roles of dynein regulatory factors remain poorly understood as a result their functional complexity and the interdependence kinesin motor activities. We used novel approach to overcome these challenges, combining acute in vivo inhibition with automated high temporal spatial resolution particle tracking. Acute nonneuronal cells caused an immediate dispersal diverse forms cargo, resulting from sharp decrease microtubule minus-end run length followed by gradual...
The microtubule-associated protein, doublecortin-like kinase 1 (DCLK1), is highly expressed in a range of cancers and prominent therapeutic target for inhibitors. physiological roles DCLK1 activity how it regulated remain elusive. Here, we analyze the role mammalian regulating microtubule binding. We found that autophosphorylates residue within its C-terminal tail to restrict prevent aberrant hyperphosphorylation microtubule-binding domain. Removal or mutation this causes an increase...
Drosophila Ensconsin/MAP7 controls spindle length, centrosome separation in brain Neuroblasts (NBs) and asymmetric transport oocytes. The control of length by Ensconsin is Kinesin-1 independent but oocyte requires targeting to microtubules Ensconsin. However, the molecular mechanism used for this remains unclear. contains a microtubule-binding domain (MBD) Kinesin-binding (KBD). Rescue experiments show that only full restores phenotype. KBD expression rescues ensc defects NBs, not fast...
Cargo transport within cells is a vital biological process that relies on the intricate interplay between motor proteins, microtubules, and complex intracellular environment. In this study, we unveil universal mechanism characterized by stick-slip motion, which governs dynamics of vesicle transport. By analyzing comprehensive dataset trajectories across various cell types environments, demonstrate cargo velocities consistently follow Gamma distribution, revealing common statistical pattern...
Cytoplasmic dynein and its regulatory proteins have been implicated in neuronal non-neuronal cell migration. A genetic model for analyzing the role of cytoplasmic specifically these processes has, however, lacking. The Loa (Legs at odd angles) mouse with a mutation heavy chain has focus an increasing number studies neuron degeneration. Despite location this tail domain chain, we previously found striking effect on coordination between two motor domains, resulting defect run length vitro...
Microtubules (MTs) are intrinsically dynamic polymers. In neurons, staggered individual microtubules form stable, polarized acentrosomal MT arrays spanning the axon and dendrite to support long-distance intracellular transport. How stability polarity of these maintained when MTs remain highly is still an open question. Here, we visualize in vivo C. elegans neurons with single resolution. We find that CRMP family homolog UNC-33 essential for neurites. unc-33 mutants, exhibit dramatically...
Abstract Phosphorylation plays a crucial role in both normal and disease processes involving the microtubule-associated protein tau. Physiologically, phosphorylation regulates tau’s subcellular localization within neurons is involved fetal development animal hibernation. However, abnormal of tau linked to formation neurofibrillary tangles (NFTs) various human tauopathies. Interestingly, patterns are similar processes, leaving unclear whether phosphorylated retains its functional processes....