A Platform for Post-translational Spatiotemporal Control of Cellular Proteins

Overview

Journal Synth Biol (Oxf)

Publisher Oxford University Press

Date 2021 Mar 25

PMID 33763602

Citations 2

Authors

Brianna Jayanthi

Bhagyashree Bachhav

Zengyi Wan

Santiago Martinez Legaspi

Laura Segatori

Affiliations

Soon will be listed here.

Abstract

Mammalian cells process information through coordinated spatiotemporal regulation of proteins. Engineering cellular networks thus relies on efficient tools for regulating protein levels in specific subcellular compartments. To address the need to manipulate the extent and dynamics of protein localization, we developed a platform technology for the target-specific control of protein destination. This platform is based on bifunctional molecules comprising a target-specific nanobody and universal sequences determining target subcellular localization or degradation rate. We demonstrate that nanobody-mediated localization depends on the expression level of the target and the nanobody, and the extent of target subcellular localization can be regulated by combining multiple target-specific nanobodies with distinct localization or degradation sequences. We also show that this platform for nanobody-mediated target localization and degradation can be regulated transcriptionally and integrated within orthogonal genetic circuits to achieve the desired temporal control over spatial regulation of target proteins. The platform reported in this study provides an innovative tool to control protein subcellular localization, which will be useful to investigate protein function and regulate large synthetic gene circuits.

Citing Articles

Targeted protein relocalization via protein transport coupling.

Ng C, Liu A, Cui B, Banik S Nature. 2024; 633(8031):941-951.

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A programmable reaction-diffusion system for spatiotemporal cell signaling circuit design.

Rajasekaran R, Chang C, Weix E, Galateo T, Coyle S Cell. 2024; 187(2):345-359.e16.

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