scholarly journals EGFR transactivates RON to drive oncogenic crosstalk

2020 ◽  
Author(s):  
Carolina Franco Nitta ◽  
Ellen W. Green ◽  
Elton D. Jhamba ◽  
Justine M. Keth ◽  
Iraís Ortiz-Caraveo ◽  
...  
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Structural Features ◽  
Single Particle Tracking ◽  
Membrane Receptors ◽  
Therapeutic Resistance ◽  
High Resolution Imaging ◽  
Oncogenic Signaling ◽  
Resolution Imaging ◽  
Stimulation Of ◽  
Formation Of Complexes

SUMMARYCrosstalk between disparate membrane receptors is thought to drive oncogenic signaling and allow for therapeutic resistance. EGFR and RON are members of two unique receptor tyrosine kinase (RTK) subfamilies that engage in crosstalk through unknown mechanisms. We combined high resolution imaging with biochemical studies and structural mutants to understand how EGFR and RON communicate. We found that EGF stimulation results in EGFR-dependent RON phosphorylation. Crosstalk is unidirectional, since MSP stimulation of RON does not trigger EGFR phosphorylation. Two-color single particle tracking captured the formation of complexes between RON and EGFR, supporting a role for direct interactions in propagating crosstalk. We further show that RON is a substrate for EGFR kinase, and transactivation of RON requires the formation of a signaling competent EGFR dimer. These results identify critical structural features of EGFR/RON crosstalk and provide new mechanistic insights into therapeutic resistance.

scholarly journals EGFR transactivates RON to drive oncogenic crosstalk

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Carolina Franco Nitta ◽  
Ellen W Green ◽  
Elton D Jhamba ◽  
Justine M Keth ◽  
Iraís Ortiz-Caraveo ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Single Particle Tracking ◽  
Membrane Microdomains ◽  
Oncogenic Signaling ◽  
Nanoscale Imaging ◽  
Resolution Imaging ◽  
Ligand Stimulation ◽  
Plasma Membrane Microdomains ◽  
Stimulation Of ◽  
Formation Of Complexes

Crosstalk between different receptor tyrosine kinases (RTKs) is thought to drive oncogenic signaling and allow therapeutic escape. EGFR and RON are two such RTKs from different subfamilies, which engage in crosstalk through unknown mechanisms. We combined high-resolution imaging with biochemical and mutational studies to ask how EGFR and RON communicate. EGF stimulation promotes EGFR-dependent phosphorylation of RON, but ligand stimulation of RON does not trigger EGFR phosphorylation – arguing that crosstalk is unidirectional. Nanoscale imaging reveals association of EGFR and RON in common plasma membrane microdomains. Two-color single particle tracking captured formation of complexes between RON and EGF-bound EGFR. Our results further show that RON is a substrate for EGFR kinase, and that transactivation of RON requires formation of a signaling competent EGFR dimer. These results support a role for direct EGFR/RON interactions in propagating crosstalk, such that EGF-stimulated EGFR phosphorylates RON to activate RON-directed signaling.

High Resolution Imaging of As-Grown Sapphire Surfaces

1985 ◽  
Vol 62 ◽  
Author(s):  
Tung Hsu ◽  
S. R. Nutt
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Structural Features ◽  
High Resolution Imaging ◽  
Sapphire Surface ◽  
Surface Steps ◽  
Transmission Electron ◽  
Reflection Electron Microscopy ◽  
Resolution Imaging ◽  
Surface Facets

ABSTRACTSurfaces of commercially grown edge-defined film-fed growth sapphire (EFG α-Al2O3) were studied in the electron microscope using both reflection electron microscopy (REM) and conventional transmission electron microscopy (TEM). The as-grown sapphire surface, ostensibly {1120}, was characterized by “rooftop” structures which were often locally periodic. These rooftop structures consisted of alternating {1120} facets and additional facets inclined a few degrees. The crystallography of the surface facets was analyzed using REM imaging of bulk specimens, and trace analysis of back-thinned plan section TEM specimens. Surface roughness was measured by stylus profilometry. and these measurements were compared to the electron microscopy observations. Fine structural features parallel to <0110> directions were also observed in both REM and TEM experiments, and these were attributed to surface steps of atomic scales.

scholarly journals Pneumatic stimulation of C. elegans mechanoreceptor neurons in a microfluidic trap

Lab on a Chip ◽  
2017 ◽  
Vol 17 (6) ◽  
pp. 1116-1127 ◽  
Author(s):  
Adam L. Nekimken ◽  
Holger Fehlauer ◽  
Anna A. Kim ◽  
Sandra N. Manosalvas-Kjono ◽  
Purim Ladpli ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
High Resolution ◽  
Neuronal Activity ◽  
High Resolution Imaging ◽  
C Elegans ◽  
Resolution Imaging ◽  
Simultaneous Immobilization ◽  
Stimulation Of

A new microfluidic tool for simultaneous immobilization, force delivery and high resolution imaging of neuronal activity in living Caenorhabditis elegans.

scholarly journals Electron cryo-tomography of vestibular hair-cell stereocilia

2018 ◽  
Author(s):  
Zoltan Metlagel ◽  
Jocelyn F Krey ◽  
Junha Song ◽  
Mark F Swift ◽  
William J Tivol ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
Hair Cell ◽  
3D Imaging ◽  
Three Dimensional ◽  
Vestibular Function ◽  
Structural Features ◽  
High Resolution Imaging ◽  
Native State ◽  
Resolution Imaging

High-resolution imaging of hair-cell stereocilia of the inner ear has contributed substantially to our understanding of auditory and vestibular function. To provide three-dimensional views of the structure of stereocilia cytoskeleton and membranes, we developed a method for rapidly freezing unfixed stereocilia on electron microscopy grids, which allowed subsequent 3D imaging by electron cryo-tomography. Structures of stereocilia tips, shafts, and tapers were revealed, demonstrating that the actin paracrystal was not perfectly ordered. This sample-preparation and imaging procedure will allow for examination of structural features of stereocilia in a near-native state.

Alternative approaches to ultra-high resolution imaging

1991 ◽  
Vol 49 ◽  
pp. 650-651
Author(s):  
J.M. Cowley
Keyword(s):  
High Resolution ◽  
High Voltage ◽  
High Resolution Electron Microscopy ◽  
Crystal Defects ◽  
High Resolution Imaging ◽  
General Applicability ◽  
Resolution Electron ◽  
Radiation Resistant ◽  
Resolution Imaging ◽  
Alternative Approaches

By extrapolation of past experience, it would seem that the future of ultra-high resolution electron microscopy rests with the advances of electron optical engineering that are improving the instrumental stability of high voltage microscopes to achieve the theoretical resolutions of 1Å or better at 1MeV or higher energies. While these high voltage instruments will undoubtedly produce valuable results on chosen specimens, their general applicability has been questioned on the basis of the excessive radiation damage effects which may significantly modify the detailed structures of crystal defects within even the most radiation resistant materials in a period of a few seconds. Other considerations such as those of cost and convenience of use add to the inducement to consider seriously the possibilities for alternative approaches to the achievement of comparable resolutions.

4-dimensional, high-resolution imaging of living cells

1992 ◽  
Vol 50 (1) ◽  
pp. 416-417
Author(s):  
Shinya Inoué
Keyword(s):  
Light Microscope ◽  
Living Cells ◽  
Live Cells ◽  
Video Tape ◽  
Active Living ◽  
High Resolution Imaging ◽  
3 Dimensional ◽  
Dynamic Architecture ◽  
Resolution Imaging ◽  
Disk Memory

This paper reports progress of our effort to rapidly capture, and display in time-lapsed mode, the 3-dimensional dynamic architecture of active living cells and developing embryos at the highest resolution of the light microscope. Our approach entails: (A) real-time video tape recording of through-focal, ultrathin optical sections of live cells at the highest resolution of the light microscope; (B) repeat of A at time-lapsed intervals; (C) once each time-lapsed interval, an image at home focus is recorded onto Optical Disk Memory Recorder (OMDR); (D) periods of interest are selected using the OMDR and video tape records; (E) selected stacks of optical sections are converted into plane projections representing different view angles (±4 degrees for stereo view, additional angles when revolving stereos are desired); (F) analysis using A - D.

Performance and applications of a field-emission gun TEM/STEM

1992 ◽  
Vol 50 (2) ◽  
pp. 942-943
Author(s):  
Judith M. Brock ◽  
Max T. Otten ◽  
Marc. J.C. de Jong
Keyword(s):  
Field Emission ◽  
High Resolution Imaging ◽  
High Quality ◽  
Small Energy ◽  
High Brightness ◽  
Small Probe ◽  
Resolution Imaging ◽  
Convergent Beam ◽  
Beam Patterns ◽  
Beam Diffraction

A Field Emission Gun (FEG) on a TEM/STEM instrument provides a major improvement in performance relative to one equipped with a LaB6 emitter. The improvement is particularly notable for small-probe techniques: EDX and EELS microanalysis, convergent beam diffraction and scanning. The high brightness of the FEG (108 to 109 A/cm2srad), compared with that of LaB6 (∼106), makes it possible to achieve high probe currents (∼1 nA) in probes of about 1 nm, whilst the currents for similar probes with LaB6 are about 100 to 500x lower. Accordingly the small, high-intensity FEG probes make it possible, e.g., to analyse precipitates and monolayer amounts of segregation on grain boundaries in metals or ceramics (Fig. 1); obtain high-quality convergent beam patterns from heavily dislocated materials; reliably detect 1 nm immuno-gold labels in biological specimens; and perform EDX mapping at nm-scale resolution even in difficult specimens like biological tissue.The high brightness and small energy spread of the FEG also bring an advantage in high-resolution imaging by significantly improving both spatial and temporal coherence.

Principle and practice of high-resolution imaging with a field-emission TEM

1992 ◽  
Vol 50 (1) ◽  
pp. 138-139
Author(s):  
Max T. Otten ◽  
Wim M.J. Coene
Keyword(s):  
High Resolution ◽  
Field Emission ◽  
Incidence Angle ◽  
Temporal Coherence ◽  
Energy Spread ◽  
High Resolution Imaging ◽  
Major Improvement ◽  
High Resolution Images ◽  
Resolution Imaging

High-resolution imaging with a LaB6 instrument is limited by the spatial and temporal coherence, with little contrast remaining beyond the point resolution. A Field Emission Gun (FEG) reduces the incidence angle by a factor 5 to 10 and the energy spread by 2 to 3. Since the incidence angle is the dominant limitation for LaB6 the FEG provides a major improvement in contrast transfer, reducing the information limit to roughly one half of the point resolution. The strong improvement, predicted from high-resolution theory, can be seen readily in diffractograms (Fig. 1) and high-resolution images (Fig. 2). Even if the information in the image is limited deliberately to the point resolution by using an objective aperture, the improved contrast transfer close to the point resolution (Fig. 1) is already worthwhile.

Imaging of ferroelectric domain walls by electron holography

1992 ◽  
Vol 50 (1) ◽  
pp. 246-247
Author(s):  
Xiao Zhang
Keyword(s):  
Magnetic Field ◽  
High Resolution ◽  
Domain Walls ◽  
Ferroelectric Domain ◽  
Object Wave ◽  
Electron Holography ◽  
High Resolution Imaging ◽  
Quantitative Measurements ◽  
Resolution Imaging ◽  
Electron Microscopes

Electron holography has recently been available to modern electron microscopy labs with the development of field emission electron microscopes. The unique advantage of recording both amplitude and phase of the object wave makes electron holography a effective tool to study electron optical phase objects. The visibility of the phase shifts of the object wave makes it possible to directly image the distributions of an electric or a magnetic field at high resolution. This work presents preliminary results of first high resolution imaging of ferroelectric domain walls by electron holography in BaTiO3 and quantitative measurements of electrostatic field distribution across domain walls.

Sign in / Sign up

Export Citation Format

Share Document