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Angewandte Chemie (International ed. in English)
09 10, 2018;57 (37): 11993-11997.

Multidirectional Activity Control of Cellular Processes by a Versatile Chemo-optogenetic Approach.

Xi Chen, Muthukumaran Venkatachalapathy, Leif Dehmelt, Yao-Wen Wu
Author Information
  1. Xi Chen: Chemical Genomics Centre of the Max Planck Society, Otto-Hahn-Str. 15, 44227, Dortmund, Germany.
  2. Muthukumaran Venkatachalapathy: Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227, Dortmund, Germany.
  3. Leif Dehmelt: Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227, Dortmund, Germany.
  4. Yao-Wen Wu: Chemical Genomics Centre of the Max Planck Society, Otto-Hahn-Str. 15, 44227, Dortmund, Germany. ORCID
PMID: 30048030 DOI: 10.1002/anie.201806976

Abstract

The spatiotemporal dynamics of proteins or organelles plays a vital role in controlling diverse cellular processes. However, acute control of activity at distinct locations within a cell is challenging. A versatile multidirectional activity control (MAC) approach is presented, which employs a photoactivatable system that may be dimerized upon chemical inducement. The system comprises second-generation SLF*-TMP (S*T) and photocaged NvocTMP-Cl dimerizers; where, SLF*-TMP features a synthetic ligand of the FKBP(F36V) binding protein, Nvoc is a caging group, and TMP is the antibiotic trimethoprim. Two MAC strategies are demonstrated to spatiotemporally control cellular signaling and intracellular cargo transport. The novel platform enables tunable, reversible, and rapid control of activity at multiple compartments in living cells.

Keywords

chemo-optogenetics intracellular transport multidirectional activity photoactivated signaling

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Grants

  1. ChemBioAP/European Research Council

MeSH Term

Dimerization
HeLa Cells
Humans
Ligands
Light
Microscopy, Confocal
Optogenetics
Peroxisomes
Tacrolimus Binding Proteins
Trimethoprim
rac1 GTP-Binding Protein

Chemicals

Ligands
RAC1 protein, human
Trimethoprim
rac1 GTP-Binding Protein
Tacrolimus Binding Proteins
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 67

Word Cloud

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