Lipid-Mediated Sequential Recruitment of Proteins Via Dual SLIPT and Dual SLIPTNVOC in Live Cells Cellular phenomena such as signal integration and transmission are based on the correct spatiotemporal organization of biomolecules within the cell. Therefore, the targeted manipul...

An excellent new protocol from Kristina Bayer and Richard Wombacher (@wombacherlab.bsky.social)! Their lipid-mediated dual SLIPT and dual SLIPT(NVOC) system offers powerful sequential control of protein recruitment in live cells. 🔬💊🔦
bio-protocol.org/en/bpdetail?...

Many thanks, Shinya!

Congratulations, beautiful work André!

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Great to see this work published in the ACS Chemical Biology special issue Lipids and Lipidation, edited by Jeremy Baskin @jeremybaskin.bsky.social and Bryan Dickinson @chembiobryan.bsky.social. (5/5)

With the photo-controllable version of dual SLIPT (dual SLIPTNVOC) we successfully prove the usefulness of the lipidomimetic for the manipulation of cellular processes in the spatiotemporal control of lamellipodia formation. (4/5)

The project was mainly fueled by the passion and enthusiasm of first author Kristina Bayer. In her work Kristina demonstrates the iterative optimization of dual SLIPT for efficiently recruiting proteins for dimerization on the inner leaflet of the PM in a light controlled, sequential manner. (3/5)

Based on Tsukiji’s SLIPT @shinyatsukiji.bsky.social technology we developed dual-SLIPT as a lipid mimic for defined, sequential protein dimerization on the inner leaflet of the plasma membrane. (2/5)

Dual SLIPT–A Lipid Mimic to Enable Spatiotemporally Defined, Sequential Protein Dimerization Spatiotemporal control of proteins is crucial for cellular phenomena such as signal integration, propagation, as well as managing crosstalk. In membrane-associated signaling, this regulation is often enabled by lipids, wherein highly dynamic, sequential recruitment of interacting proteins is key to successful signaling. Here, we present dual SLIPT (self-localizing ligand-induced protein translocation), a lipid-analog tool, capable of emulating this lipid-mediated sequential recruitment of any two proteins of interest. Dual SLIPT self-localizes to the inner leaflet of the plasma membrane (PM). There, dual SLIPT presents trimethoprim (TMP) and HaloTag ligand (HTL) to cytosolic proteins of interest (POIs), whereupon POIs fused to the protein tags iK6eDHFR, or to HOB are recruited. A systematic extension of the linkers connecting the two mutually orthogonal headgroups was implemented to overcome the steric clash between the recruited POIs. Using Förster resonance energy transfer (FRET), we verify that the resulting probe is capable of simultaneous binding of both proteins of interest, as well as their dimerization. Dual SLIPT was found to be particularly suitable for use in physiologically relevant concentrations, such as recruitment via tightly regulated, transient lipid species. We further expanded dual SLIPT to the photocontrollable dual SLIPTNVOC, by introducing a photocaging group onto the TMP moiety. Dual SLIPTNVOC enables sequential and spatiotemporally defined dimerization upon blue light irradiation. Thus, dual SLIPTNVOC serves as a close mimic of physiology, enabling interrogation of dynamic cytosol-to-plasma membrane recruitment events and their impact on signaling.

Happy to share our new publication in ACS Chemical Biology @pubs.acs.org reporting a new chemical biology tool – dual SLIPT! Congratulations to first author Kristina Bayer @XXX, all co-authors and collaborator Shige Yoshimura @XXX. Open Access:
pubs.acs.org/doi/10.1021/... (1/5)

Congratulations to the first author Philipp Pöschko, master student Caroline Berrou and all co-authors. Special thanks also to Kaisa Pakari and Jochen Wittbrodt for the wonderful collaboration. I am very grateful for the enthusiasm and commitment of everyone involved!

Photoactivatable Plant Hormone-Based Chemical Inducers of Proximity for In Vivo Applications Protein interactions play a crucial role in regulating cellular mechanisms, highlighting the need for effective methods to control these processes. In this regard, chemical inducers of proximity (CIPs...

Happy to start our new bsky.social channel with a recent publication from our lab: Photoinduced protein proximity using novel CIPs - in vivo application in medaka embryos. Check out at ACS Chemical Biology: pubs.acs.org/doi/full/10....
#CIP#chemicalinducerofproximity #photocontrol#chemicalbiology