Analysis of Biomolecular Condensates in Membrane Receptor Signaling

CD BioSciences is dedicated to the broad functional characterization of biomolecular condensates to develop a range of regulatory targets and approaches to provide new opportunities for drug development and clinical treatment of disease. Here, CD BioSciences offers professional services to analyze the function of biomolecular condensates in membrane receptor signaling for the development of drug targets.

Introduction

Clustering is a distinctive feature of plasma membrane (PM) receptors. Multiple mechanisms may lead to receptor clustering, such as dimerization, oligomerization and complex formation, co-localization within nanodomains, and cortical cytoskeleton-mediated clustering. Recently, it has been shown that liquid-liquid phase separation (LLPS) of proteins at the PM is emerging as a new clustering mechanism. Receptor/transmembrane signaling proteins can be core components necessary for LLPS or clients enriched in phase separation condensates. Different families of membrane receptors, such as receptor tyrosine kinases (RTK), cell adhesion receptors and immune cell receptors, are able to transform from freely diffusing monomers or discrete dimers to higher order oligomers with uncertain stoichiometry. Organizing receptors into clusters that can extend to hundreds of nanometers plays an important role in downstream signaling.

Fig. 1. Two classes of phase-separated condensates at the PM. (Jaqaman K, et al., 2021)

Customized Services

Biomolecular condensates regulate signaling in a variety of ways, including by increasing protein binding affinity and by modulating the local biochemical environment. We have advanced quantitative optical microscopy to probe their properties and signal regulation in the cell. In addition, we offer active biosensors capable of monitoring molecular activity in living cells with high spatial and temporal resolution, widely used to study the signaling consequences of LLPS.

CD BioSciences is committed to analyzing different types of condensates in PM to explore their signaling and functional consequences.

• Analysis of condensates of transmembrane proteins and signaling partners
  We can analyze the role of plasma membrane receptor-mediated protein condensates in signaling, particularly RTK. LLPS involving RTK are governed by the charged environment and, in addition, can impose additional levels of regulation on signaling by excluding proteins that may trigger aberrant pathological signals. Based on the analysis of RTK function, we aim to design small molecules targeting RTK for drug development.
• Analysis of condensates of scaffolding proteins that help organize receptors
  Phase-separated proteins are scaffolding proteins that organize receptors on PM and are essential for downstream signaling. We can analyze the role of LLPS of these scaffolding proteins in presynaptic boutons, cell polarity and receptor signaling pathways.
• Analysis of modular condensates that assist with signaling at the PM
  The small GTPases GIT and PIX, which mediate signaling just downstream of proteins affiliated with focal adhesions, cell junctions, and the PSD. We can analyze the role of LLPS of GIT/PIX proteins in cell signaling.

We can reconstruct membrane-associated condensates in vitro to analyze the function of these condensates in controlling signaling pathways. Here, we provide quantitative light microscopy experiments combined with mathematical modeling and control system manipulation to gain deeper insight into the functional and signaling consequences of membrane-associated condensates formation and regulation. Investigating cellular signaling through the lens of phase separation may define new approaches to drug intervention. If you have any special requirements for our services, please feel free to contact us. We are looking forward to working together with your attractive projects.