Abstract：
:Electron microscopy (EM) remains the primary method for imaging cellular and tissue ultrastructure, although simultaneous localization of multiple specific molecules continues to be a challenge for EM. We present a method for obtaining multicolor EM views of multiple subcellular components. The method uses sequential, localized deposition of different lanthanides by photosensitizers, small-molecule probes, or peroxidases. Detailed view of biological structures is created by overlaying conventional electron micrographs with pseudocolor lanthanide elemental maps derived from distinctive electron energy-loss spectra of each lanthanide deposit via energy-filtered transmission electron microscopy. This results in multicolor EM images analogous to multicolor fluorescence but with the benefit of the full spatial resolution of EM. We illustrate the power of this methodology by visualizing hippocampal astrocytes to show that processes from two astrocytes can share a single synapse. We also show that polyarginine-based cell-penetrating peptides enter the cell via endocytosis, and that newly synthesized PKMζ in cultured neurons preferentially localize to the postsynaptic membrane.
journal_name
Cell Chem Bioljournal_title
Cell chemical biologyauthors
Adams SR,Mackey MR,Ramachandra R,Palida Lemieux SF,Steinbach P,Bushong EA,Butko MT,Giepmans BNG,Ellisman MH,Tsien RYdoi
10.1016/j.chembiol.2016.10.006subject
Has Abstractpub_date
2016-11-17 00:00:00pages
1417-1427issue
11eissn
2451-9456issn
2451-9448pii
S2451-9456(16)30357-9journal_volume
23pub_type
杂志文章abstract：:Rational design of drug-like small-molecule ligands based on structural information of proteins remains a significant challenge in chemical biology. In particular, designs targeting protein-protein interfaces have met little success given the dynamic nature of the protein surfaces. Herein, we utilized the structure of...
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abstract：:Increased telomerase activity is associated with malignancy and poor prognosis in human cancer, but the development of targeted agents has not yet provided clinical benefit. Here we report that, instead of targeting the telomerase enzyme directly, small molecules that bind to the G-hairpin of the hTERT G-quadruplex-fo...
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journal_title：Cell chemical biology
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doi：10.1016/j.chembiol.2018.06.013
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
pub_type： 杂志文章
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
pub_type： 杂志文章
doi：10.1016/j.chembiol.2018.02.003
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journal_title：Cell chemical biology
pub_type： 杂志文章
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abstract：:Recent advances in induced pluripotent stem cell technologies and phenotypic screening shape the future of bioactive small-molecule discovery. In this review we analyze the impact of small-molecule phenotypic screens on drug discovery as well as on the investigation of human development and disease biology. We further...
journal_title：Cell chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.chembiol.2019.05.007
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abstract：:Ubiquinone (UQ) is a conserved polyprenylated lipid essential to cellular respiration. Two papers, one in this issue of Cell Chemical Biology (Hajj Chehade et al., 2019) and another in Molecular Cell (Lohman et al., 2019), identify lipid-binding proteins that play crucial roles in chaperoning UQ-intermediates. ...
journal_title：Cell chemical biology
pub_type： 评论,杂志文章
doi：10.1016/j.chembiol.2019.04.005
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