A photosensitive degron enables acute light-induced protein degradation in the nervous system

Current Biology : CB
Anke HermannAlexander Gottschalk

Abstract

Acutely inducing degradation enables studying the function of essential proteins. Available techniques target proteins post-translationally, via ubiquitin or by fusing destabilizing domains (degrons), and in some cases degradation is controllable by small molecules. Yet, they are comparably slow, possibly inducing compensatory changes, and do not allow localized protein depletion. The photosensitizer miniature singlet oxygen generator (miniSOG), fused to proteins of interest, provides fast light-induced protein destruction, e.g. affecting neurotransmission within minutes, but the reactive oxygen species (ROS) generated also affect proteins nearby, causing multifaceted phenotypes. A photosensitive degron (psd), recently developed and characterized in yeast, only targets the protein it is fused to, acting quickly as it is ubiquitin-independent, and the B-LID light-inducible degron was similarly shown to affect protein abundance in zebrafish. We implemented the psd in Caenorhabditis elegans and compared it to miniSOG. The psd effectively caused protein degradation within one hour of low intensity blue light (30 μW/mm(2)). Targeting synaptotagmin (SNT-1::tagRFP::psd), required for efficient neurotransmission, reduced locomotion wit...Continue Reading

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Citations

Feb 19, 2016·Applied Microbiology and Biotechnology·Christian Renicke, Christof Taxis
Nov 1, 2016·Nature Reviews. Genetics·Benjamin E HousdenNorbert Perrimon
Nov 28, 2017·Annual Review of Genetics·Toyoaki Natsume, Masato T Kanemaki
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Jan 18, 2020·Nature Communications·Wen DengHeinrich Leonhardt
Aug 14, 2019·Genetics·Jeremy Nance, Christian Frøkjær-Jensen
Aug 11, 2020·Journal of Neurogenetics·Joseph J H LiangCatharine H Rankin
Feb 2, 2021·Current Protocols·Nikita S DivekarSarah M Wignall
Apr 3, 2021·Cell Stem Cell·Qiang HuangXiling Shen
Apr 6, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Brecht DriesschaertLiesbet Temmerman
May 27, 2021·Nature Chemical Biology·Geng-Yuan Chen, Michael A Lampson
Jun 12, 2021·Cell Chemical Biology·Martin Reynders, Dirk Trauner
Jul 10, 2018·Chemical Reviews·Aba LosiAndreas Möglich
Nov 3, 2017·Neuron·Benjamin R RostPeter Hegemann

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