scholarly journals Microtubule-directed transport of purine metabolons drives their cytosolic transit to mitochondria

2018 ◽  
Vol 115 (51) ◽  
pp. 13009-13014 ◽  
Author(s):  
Chung Yu Chan ◽  
Anthony M. Pedley ◽  
Doory Kim ◽  
Chenglong Xia ◽  
Xiaowei Zhuang ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Biosynthetic Pathway ◽  
De Novo ◽  
Microtubule Depolymerization ◽  
Directed Motion ◽  
Time Resolved ◽  
Superresolution Imaging ◽  
Directed Transport ◽  
Time Resolved Imaging ◽  
Localization Time

To meet their purine demand, cells activate the de novo purine biosynthetic pathway and transiently cluster the pathway enzymes into metabolons called purinosomes. Recently, we have shown that purinosomes were spatially colocalized with mitochondria and microtubules, yet it remained unclear as to what drives these associations and whether a relationship between them exist. Here, we employed superresolution imaging methods to describe purinosome transit in the context of subcellular localization. Time-resolved imaging of purinosomes showed that these assemblies exhibit directed motion as they move along a microtubule toward mitochondria, where upon colocalization, a change in purinosome motion was observed. A majority of purinosomes colocalized with mitochondria were also deemed colocalized with microtubules. Nocodazole-dependent microtubule depolymerization resulted in a loss in the purinosome–mitochondria colocalization, suggesting that the association of purinosomes with mitochondria is facilitated by microtubule-directed transport, and thereby supporting our notion of an interdependency between these subcellular components in maximizing purine production through the de novo purine biosynthetic pathway.

scholarly journals Giant enhancement of THz-frequency optical nonlinearity by phonon polariton in ionic crystals

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yao Lu ◽  
Qi Zhang ◽  
Qiang Wu ◽  
Zhigang Chen ◽  
Xueming Liu ◽  
...  
Keyword(s):  
Near Infrared ◽  
Optical Nonlinearity ◽  
Ionic Crystals ◽  
Nonlinear Optical Susceptibility ◽  
Time Resolved ◽  
Light Coupling ◽  
Tremendous Progress ◽  
Fundamental Research ◽  
Ionic Contribution ◽  
Time Resolved Imaging

AbstractThe field of nonlinear optics has grown substantially in past decades, leading to tremendous progress in fundamental research and revolutionized applications. Traditionally, the optical nonlinearity for a light wave at frequencies beyond near-infrared is observed with very high peak intensity, as in most materials only the electronic nonlinearity dominates while ionic contribution is negligible. However, it was shown that the ionic contribution to nonlinearity can be much larger than the electronic one in microwave experiments. In the terahertz (THz) regime, phonon polariton may assist to substantially trigger the ionic nonlinearity of the crystals, so as to enhance even more the nonlinear optical susceptibility. Here, we experimentally demonstrate a giant second-order optical nonlinearity at THz frequency, orders of magnitude higher than that in the visible and microwave regimes. Different from previous work, the phonon-light coupling is achieved under a phase-matching setting, and the dynamic process of nonlinear THz generation is directly observed in a thin-film waveguide using a time-resolved imaging technique. Furthermore, a nonlinear modification to the Huang equations is proposed to explain the observed nonlinearity enhancement. This work brings about an effective approach to achieve high nonlinearity in ionic crystals, promising for applications in THz nonlinear technologies.

scholarly journals Subcellular localization-dependent changes in EGFP fluorescence lifetime measured by time-resolved flow cytometry

2013 ◽  
Vol 4 (8) ◽  
pp. 1390 ◽  
Author(s):  
Ali Vaziri Gohar ◽  
Ruofan Cao ◽  
Patrick Jenkins ◽  
Wenyan Li ◽  
Jessica P. Houston ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Subcellular Localization ◽  
Fluorescence Lifetime ◽  
Time Resolved ◽  
Egfp Fluorescence

scholarly journals Time-resolved imaging refractometry of microbicidal films using quantitative phase microscopy

2011 ◽  
Vol 16 (12) ◽  
pp. 120510 ◽  
Author(s):  
Matthew T. Rinehart ◽  
Tyler K. Drake ◽  
Francisco E. Robles ◽  
Lisa C. Rohan ◽  
David Katz ◽  
...  
Keyword(s):  
Time Resolved ◽  
Quantitative Phase ◽  
Phase Microscopy ◽  
Quantitative Phase Microscopy ◽  
Time Resolved Imaging

scholarly journals Time-Resolved Imaging of Electrochemical Switching in Nanoscale Resistive Memory Elements

2015 ◽  
Vol 21 (S3) ◽  
pp. 1911-1912
Author(s):  
William A. Hubbard ◽  
E. R. White ◽  
Alexander Kerelsky ◽  
G. Jasmin ◽  
Jared J. Lodico ◽  
...  
Keyword(s):  
Resistive Memory ◽  
Time Resolved ◽  
Time Resolved Imaging

scholarly journals Two-Photon Time-Gated In Vivo Imaging of Dihydrolipoic-Acid-Decorated Gold Nanoclusters

Materials ◽  
2021 ◽  
Vol 14 (24) ◽  
pp. 7744
Author(s):  
Ye Tian ◽  
Ming Wei ◽  
Lijun Wang ◽  
Yuankai Hong ◽  
Dan Luo ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Gold Nanoclusters ◽  
Photon Absorption ◽  
Gold Nanocluster ◽  
Time Resolved ◽  
Dihydrolipoic Acid ◽  
Two Photon Absorption ◽  
Two Photon ◽  
Time Resolved Imaging

Due to the unique advantages of two-photon technology and time-resolved imaging technology in the biomedical field, attention has been paid to them. Gold clusters possess excellent physicochemical properties and low biotoxicity, which make them greatly advantageous in biological imaging, especially for in vivo animal imaging. A gold nanocluster was coupled with dihydrolipoic acid to obtain a functionalized nanoprobe; the material displayed significant features, including a large two-photon absorption cross-section (up to 1.59 × 105 GM) and prolonged fluorescence lifetime (>300 ns). The two-photon and time-resolution techniques were used to perform cell imaging and in vivo imaging.

scholarly journals The biosynthetic origin of psychoactive kavalactones in kava

2018 ◽  
Author(s):  
Tomáš Pluskal ◽  
Michael P. Torrens-Spence ◽  
Timothy R. Fallon ◽  
Andrea De Abreu ◽  
Cindy H. Shi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Biosynthetic Pathway ◽  
Chalcone Synthase ◽  
De Novo ◽  
Piper Methysticum ◽  
Heterologous Production ◽  
Traditional Use ◽  
Plant Biochemistry ◽  
Tailoring Enzymes

AbstractFor millennia, humans have used plants for medicinal purposes. However, our limited understanding of plant biochemistry hinders the translation of such ancient wisdom into modern pharmaceuticals1. Kava (Piper methysticum) is a medicinal plant native to the Polynesian islands with anxiolytic and analgesic properties supported by over 3,000 years of traditional use as well as numerous recent clinical trials2–5. The main psychoactive principles of kava, kavalactones, are a unique class of polyketide natural products known to interact with central nervous system through mechanisms distinct from those of the prescription psychiatric drugs benzodiazepines and opioids6,7. Here we reportde novoelucidation of the biosynthetic pathway of kavalactones, consisting of seven specialized metabolic enzymes. Based on phylogenetic and crystallographic analyses, we highlight the emergence of two paralogous styrylpyrone synthases, both of which have neofunctionalized from an ancestral chalcone synthase to catalyze the formation of the kavalactone scaffold. Structurally diverse kavalactones are then biosynthesized by subsequent regio- and stereo-specific tailoring enzymes. We demonstrate the feasibility of engineering heterologous production of kavalactones and their derivatives in bacterial, yeast, and plant hosts, thus opening an avenue towards the development of new psychiatric therapeutics for anxiety disorders, which affect over 260 million people globally8.

scholarly journals The C-terminal helix 9 motif in rat cannabinoid receptor type 1 regulates axonal trafficking and surface expression

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Alexandra Fletcher-Jones ◽  
Keri L Hildick ◽  
Ashley J Evans ◽  
Yasuko Nakamura ◽  
Kevin A Wilkinson ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Secretory Pathway ◽  
Cannabinoid Receptor ◽  
Surface Expression ◽  
Surface Polarity ◽  
Time Resolved ◽  
Surface Stability ◽  
C Terminus ◽  
Time Resolved Imaging ◽  
Dual Mechanism

Cannabinoid type one receptor (CB1R) is only stably surface expressed in axons, where it downregulates neurotransmitter release. How this tightly regulated axonal surface polarity is established and maintained is unclear. To address this question, we used time-resolved imaging to determine the trafficking of CB1R from biosynthesis to mature polarised localisation in cultured rat hippocampal neurons. We show that the secretory pathway delivery of CB1R is axonally biased and that surface expressed CB1R is more stable in axons than in dendrites. This dual mechanism is mediated by the CB1R C-terminus and involves the Helix 9 (H9) domain. Removal of the H9 domain increases secretory pathway delivery to dendrites and decreases surface stability. Furthermore, CB1RΔH9 is more sensitive to agonist-induced internalisation and less efficient at downstream signalling than CB1RWT. Together, these results shed new light on how polarity of CB1R is mediated and indicate that the C-terminal H9 domain plays key roles in this process.

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