TY - JOUR
T1 - Synthesis and Cellular Labeling of Multifunctional Phosphatidylinositol Bis- and Trisphosphate Derivatives
AU - Müller, Rainer
AU - Kojic, Ana
AU - Citir, Mevlut
AU - Schultz, Carsten
N1 - Funding Information:
We gratefully acknowledge funding from the NIH (R01GM127631) and Transregio 186, funded by the German Research Foundation (DFG). We thank the EMBL proteomics facility for the analysis of the proteomics data, especially Dr Per Haberkant and Dr Frank Stein. We also thank Dr Sergio Triana for his help with the creation of the heat map plots. Open access funding enabled and organized by Projekt DEAL.
Funding Information:
We gratefully acknowledge funding from the NIH (R01GM127631) and Transregio 186, funded by the German Research Foundation (DFG). We thank the EMBL proteomics facility for the analysis of the proteomics data, especially Dr Per Haberkant and Dr Frank Stein. We also thank Dr Sergio Triana for his help with the creation of the heat map plots. Open access funding enabled and organized by Projekt DEAL.
Publisher Copyright:
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
PY - 2021/9/1
Y1 - 2021/9/1
N2 - We synthesized the first multifunctionalized phosphoinositide polyphosphate derivatives featuring a photo-removable protecting group (“cage”), a photo-crosslinkable diazirine group, and a terminal alkyne group useful for click chemistry. We demonstrate that the lipid derivatives readily enter cells. After photo-crosslinking, cell fixation and fluorescent tagging via click chemistry, we determined the intracellular location of the lipid derivatives before and after uncaging of the lipids. We find that there is rapid trafficking of PI(3,4)P2 and PI(3,4,5)P3 derivatives to the plasma membrane, opening the intriguing possibility that there is active transport of these lipids involved. We employed the photo-crosslinking and click chemistry functions to analyze the proteome of PI(3,4,5)P3-binding proteins. From the latter, we validated by RNAi that the putative lipid binding proteins ATP11A and MPP6 are involved in the transport of PI(3,4,5)P3 to the plasma membrane.
AB - We synthesized the first multifunctionalized phosphoinositide polyphosphate derivatives featuring a photo-removable protecting group (“cage”), a photo-crosslinkable diazirine group, and a terminal alkyne group useful for click chemistry. We demonstrate that the lipid derivatives readily enter cells. After photo-crosslinking, cell fixation and fluorescent tagging via click chemistry, we determined the intracellular location of the lipid derivatives before and after uncaging of the lipids. We find that there is rapid trafficking of PI(3,4)P2 and PI(3,4,5)P3 derivatives to the plasma membrane, opening the intriguing possibility that there is active transport of these lipids involved. We employed the photo-crosslinking and click chemistry functions to analyze the proteome of PI(3,4,5)P3-binding proteins. From the latter, we validated by RNAi that the putative lipid binding proteins ATP11A and MPP6 are involved in the transport of PI(3,4,5)P3 to the plasma membrane.
KW - caged compounds
KW - cell imaging
KW - lipid transport
KW - phosphoinositides
KW - photo-crosslinking
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U2 - 10.1002/anie.202103599
DO - 10.1002/anie.202103599
M3 - Article
C2 - 34075669
AN - SCOPUS:85107651246
SN - 1433-7851
VL - 60
SP - 19759
EP - 19765
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 36
ER -