Common Receptor Research Articles

EPFL peptide signalling ensures robust self-pollination success under cool temperature stress by aligning the length of the stamen and pistil.

Successful sexual reproduction of plants requires temperature-sensitive processes, and temperature stress sometimes causes developmental asynchrony between male and female reproductive tissues. In Arabidopsis thaliana, self-pollination occurs when the stamen and pistil lengths are aligned in a single flower so that pollens at the stamen tip are delivered to the stigma at the pistil tip. Although intercellular signalling acts in several reproduction steps, how signalling molecules, including secreted peptides, contribute to the synchronous growth of reproductive tissues remains limited. Here, we show that the mutant of the secreted peptide EPIDERMAL PATTERNING FACTOR LIKE 6 (EPFL6), which shows no phenotypes at a moderate temperature, fails in fruit production at a cool temperature due to insufficient elongation of stamens. EPFL6 is expressed in stamen filaments and promotes filament elongation to achieve the alignment of stamen and pistil lengths at a cool temperature. We also found that, at a moderate temperature, all EPFL6-subfamily genes are required for stamen elongation. Furthermore, we showed that ERECTA (ER), known as a common receptor for EPFL-family peptides, mediates the stamen-pistil growth coordination. Lastly, we provided evidence that modulation of ER activity rescues the reproduction failure caused by insufficient stamen elongation by realigning the stamen and pistil lengths.

SARS-CoV-2 Delta Variant: Interplay between Individual Mutations and Their Allosteric Synergy.

Since its first appearance in April 2021, B.1.617.2, also termed variant Delta, catalyzed one major worldwide wave dominating the second year of coronavirus disease 2019 (COVID-19) pandemic. Despite its quick disappearance worldwide, the strong virulence caused by a few point mutations remains an unsolved problem largely. Along with the other two sublineages, the Delta variant harbors an accumulation of Spike protein mutations, including the previously identified L452R, E484Q, and the newly emerged T478K on its receptor binding domain (RBD). We used molecular dynamics (MD) simulations, in combination with free energy perturbation (FEP) calculations, to examine the effects of two combinative mutation sets, L452R + E484Q and L452R + T478K. Our dynamic trajectories reveal an enhancement in binding affinity between mutated RBD and the common receptor protein angiotensin converting enzyme 2 (ACE2) through a net increase in the buried molecular surface area of the binary complex. This enhanced binding, mediated through Gln493, sets the same stage for all three sublineages due to the presence of L452R mutation. The other mutation component, E484Q or T478K, was found to impact the RBD-ACE2 binding and help the variant to evade several monoclonal antibodies (mAbs) in a distinct manner. Especially for L452R + T478K, synergies between mutations are mediated through a complex residual and water interaction network and further enhance its binding to ACE2. Taking together, this study demonstrates that new variants of SARS-CoV-2 accomplish both "attack" (infection) and "defense" (antibody neutralization escape) with the same "polished sword" (mutated Spike RBD).

186 Dissecting the role of the common neurotrophin receptor CD271 in the skin: generation and characterization of a novel mouse model with keratinocyte-specific conditional deletion

The common neurotrophin receptor CD271, also called p75NTR, is the transmembrane low-affinity receptor for neurotrophins, belonging to the TNF superfamily. In the skin, CD271 is involved in the differentiation process and seems like to be implicated in cutaneous pathogenesis. To date, different animal models have been developed to obtain null mutations of CD271, but they defy to explain CD271 precise role in keratinocytes. By using a Keratin14-Cre mediated excision of the CD271 gene flanked by loxP sites, we generated a novel mouse model with a conditional deletion of CD271 in the epidermis.

Interleukin-17 Promotes the Infiltration of CD8+ T Cells into the Brain in a Mouse Model for Alzheimer’s Disease

ABSTRACT Background Interleukin-17 (IL-17) family cytokines play critical roles in inflammation and pathogen resistance. Inflammation in the central nervous system, denoted as neuroinflammation, promotes the onset and progression of Alzheimer’s disease (AD). Previous studies showed that IL-17A neutralizing antibody treatment alleviated Amyloid β (Aβ) burden in rodent models of AD, while overexpression of IL-17A in mouse lateral ventricles rescued part of the AD pathology. However, the involvement of IL-17 in AD and its mechanism of action remain largely unknown. Methods To investigate the role of IL-17 in AD, we crossed mice lacking the common receptor of IL-17 signaling (IL-17RA knockout mice) to the APP/PS1 mouse model of AD. We then analyzed the composition of immune cells and cytokines/chemokines during different phases of AD pathology, and interrogated the underlying mechanism by which IL-17 may regulate immune cell infiltration into AD brains. Results Ablation of IL-17RA in APP/PS1 mice decreased infiltration of CD8+ T cells and myeloid cells to mouse brain. IL-17 was able to promote the production of myeloid- and T cell-attracting chemokines CXCL1 and CXCL9/10 in primary glial cells. We also observed that IL-17 is upregulated in the late stage of AD development, and ectopic expression of IL-17 via adenoviral infection to the cortex trended towards worsened cognition in APP/PS1 mice, suggesting a pathogenic role of excessive IL-17 in AD. Conclusion Our data show that IL-17 signaling promotes neuroinflammation in AD by accelerating the infiltration of CD8+ T lymphocytes and Gr1+ CD11b+ myeloid cells.

Comprehensive analysis of human IL-4 receptor subunits shows compartmentalization in steady state and dupilumab treatment.

Insight into the pathomechanism of atopic diseases demonstrated a pivotal role of the cytokines interleukin-4 (IL-4) and IL-13, which has spurred the development of tailored therapeutics targeting their common IL-4 receptor (IL-4R). However, several aspects of the IL-4R system remain ill-defined in humans. We used multicolor spectral flow cytometry to characterize IL-4R subunit expression in 28 human immune cell subsets on protein and mRNA levels and assessed their subcellular distribution by applying a specifically adapted protocol that avoided influence of fixation and permeabilization on fluorochrome and antibody performance. In patients, we investigated possible changes in IL-4Rα distribution before and during treatment with dupilumab, a monoclonal antibody-targeting IL-4Rα. Whereas all immune cell subsets investigated expressed IL-4Rα and common γ chain protein and mRNA, expression of IL-13Rα1 was restricted to myeloid and B cells. Interestingly, some cells contained considerably more intracellular IL-4R protein than on their surface. Naive B cells were found to carry the highest levels of IL-4Rα distributed evenly between surface and intracellular space, whereas IL-4Rα was found predominantly in intracellular pools in neutrophils. In patients with atopic diseases treated with dupilumab, we observed that engagement of IL-4Rα by dupilumab resulted in internalization of the antibody and decreased total IL-4Rα expression. Notably, even after months of treatment not all intracellular IL-4Rα molecules were occupied by dupilumab, indicating the presence of a "dormant" intracellular IL-4Rα pool that could be mobilized upon certain extrinsic or intrinsic cues. Collectively, our findings suggest that distinct human immune cell subsets contain surface and intracellular IL-4R pools, which are differently affected by targeted biologic treatment.

The ocular manifestations of novel coronavirus: A literature review

Apart from the systemic cardinal symptoms such as fever, cough, fatigue, headache, and diarrhea, ocular symptoms have gained much importance during the peak hours of the COVID pandemic. Since an exposed ocular surface can act as a gateway for various respiratory viruses, there is an increased interest in exploring the ocular route of transmission and viral RNA detection in ocular fluids. Moreover, the ocular surface can also share some common viral binding receptors. A large number of case reports and observational studies have been published so far reporting anterior, posterior, orbital, and neurological complications of the eye and orbit. Ocular complications can range from mild self-limiting pathologies such as conjunctivitis, episcleritis, and retinal cotton wool spots to severe blinding pathologies such as mucormycosis, retinal vessel occlusions, candida retinitis, and optic neuritis. There is an increased risk of corneal graft rejection and reactivation of certain microorganisms post severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccination. The present narrative review provides a brief overview of the current literature and an in-depth understanding of the ocular implications of SARS-CoV-2.

Regulation of Off-track bidirectional signaling by Semaphorin-1a and Wnt signaling in the Drosophila motor axon guidance

Off-track receptor tyrosine kinase (OTK) has been shown to play an important role in the Drosophila motor axon pathfinding. The results of biochemical and genetic interactions previously suggested that OTK acts as a component of Semaphorin-1a/Plexin A (Sema-1a/PlexA) signaling during embryonic motor axon guidance and further showed that OTK binds to Wnt family members Wnt2 and Wnt4 and their common receptor Frizzled (Fz). However, the molecular mechanisms underlying the motor axon guidance function of OTK remain elusive. Here, we conclude that OTK mediates the forward and reverse signaling required for intersegmental nerve b (ISNb) motor axon pathfinding and we also demonstrate that the loss of two copies of Sema-1a synergistically enhances the bypass phenotype observed in otk mutants. Furthermore, the amorphic wnt2 mutation resulted in increased premature branching phenotypes, and the loss of fz function caused a frequent inability of ISNb motor axons to defasciculate at specific choice points. Consistent with a previous study, wnt4 mutant axons were often defective in recognizing target muscles. Interestingly, the bypass phenotype of otk mutants was robustly suppressed by loss of function mutations in wnt2, wnt4, or fz. In contrast, total ISNb defects of otk were increased by the loss-of-function alleles in wnt2 and wnt4, but not fz. These findings indicate that OTK may participate in the crosstalk between the Sema-1a/PlexA and Wnt signaling pathways, thereby contributing to ISNb motor axon pathfinding and target recognition.

Effects of 3-octen-2-one on human olfactory receptor responses to vanilla flavor.

Most of the odors that humans perceive daily are complex odors. It is believed that the modulation, enhancement, and suppression of overall complex odors are caused by interactions between odor molecules. In this study, to understand the interaction between odor molecules at the level of human olfactory receptor responses, the effects of 3-octen-2-one, which has been shown to modulate vanilla flavors, were analyzed using a human olfactory receptor sensor that uses all human olfactory receptors (388 types) as sensing molecules. As a result, the response intensity of 1 common receptor (OR1D2) was synergistically enhanced in vanilla flavor with 3-octen-2-one compared with vanilla flavor, and the response of 1 receptor (OR5K1) to vanilla flavor was completely suppressed. These results strongly suggested that the response of human olfactory receptors to complex odors is enhanced or suppressed by relatively few other odor molecules.

Lipid Nanoparticles-The Future Treatment of Diabetes Mellitus and Triple-Negative Breast Cancer

Lipid nanoparticles are a promising new way of treating many diseases. Diabetes Mellitus is when one has increased blood glucose levels. It’s a prevalent disease with millions of people in the U.S being diagnosed with it. The common antidiabetic drug called Metformin is currently the main drug being used for the treatment of diabetes and is taken two or three times daily. Researchers looked at nanomedicine as a potential new medicinal agent for the management of diabetes that will still give similar results to Metformin and need a lower dose. They saw that combining the compounds glycyrrhizin and thymoquinone into a nanoparticle called GT has been shown to significantly reduce blood glucose levels in rats more than when compared to their individual forms. This combined nanoformulation required inexpensive chemicals just like Metformin and only needed to be administered once daily, so was successful in being a new option for the treatment of diabetes mellitus. Another disease nanomedicine can be used to treat is breast cancer. This disease is more commonly seen in women and is when the cells of the breast begin to divide uncontrollably. Triple-negative breast cancer is a more complicated form of breast cancer since it doesn't have any of the common receptors used to target the disease. Researchers turned to nanomedicine to treat this form of breast cancer as normal chemotherapy was ineffective. They combined a TGF-B inhibitor called Tranilast which is an approved anti-fibrotic and antihistamine drug with Doxil nanomedicine. This was shown to normalize the tumor microenvironment, increase perfusion and oxygenation, and enhance anti-tumor immunity. Both nanomedicine approaches show how lipid nanoparticles can pave the road for the future treatment of these diseases.

734MO Deep sequencing of the T-cell receptor reveals common and reproducible CD8 T-cell receptor signatures of response to checkpoint immunotherapy

Immune checkpoint blockade (ICB) has revolutionized the treatment of metastatic melanoma (MM). However, robust biomarkers of response and the identity of key antigenic targets remains lacking. We have previously demonstrated the importance of large peripheral CD8+ T cell clones in the ICB response; these clones being more cytotoxic and especially sensitive to ICB. However, identifying key groups of T cells based on their T cell receptor (TCR) usage has remained elusive.

High activity of an affinity-matured ACE2 decoy against Omicron SARS-CoV-2 and pre-emergent coronaviruses.

The viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly its cell-binding spike protein gene, has undergone rapid evolution during the coronavirus disease 2019 (COVID-19) pandemic. Variants including Omicron BA.1 and Omicron BA.2 now seriously threaten the efficacy of therapeutic monoclonal antibodies and vaccines that target the spike protein. Viral evolution over a much longer timescale has generated a wide range of genetically distinct sarbecoviruses in animal populations, including the pandemic viruses SARS-CoV-2 and SARS-CoV-1. The genetic diversity and widespread zoonotic potential of this group complicates current attempts to develop drugs in preparation for the next sarbecovirus pandemic. Receptor-based decoy inhibitors can target a wide range of viral strains with a common receptor and may have intrinsic resistance to escape mutant generation and antigenic drift. We previously generated an affinity-matured decoy inhibitor based on the receptor target of the SARS-CoV-2 spike protein, angiotensin-converting enzyme 2 (ACE2), and deployed it in a recombinant adeno-associated virus vector (rAAV) for intranasal delivery and passive prophylaxis against COVID-19. Here, we demonstrate the exceptional binding and neutralizing potency of this ACE2 decoy against SARS-CoV-2 variants including Omicron BA.1 and Omicron BA.2. Tight decoy binding tracks with human ACE2 binding of viral spike receptor-binding domains across diverse clades of coronaviruses. Furthermore, in a coronavirus that cannot bind human ACE2, a variant that acquired human ACE2 binding was bound by the decoy with nanomolar affinity. Considering these results, we discuss a strategy of decoy-based treatment and passive protection to mitigate the ongoing COVID-19 pandemic and future airway virus threats.

In vivo nanoscopic landscape of neurexin ligands underlying anterograde synapse specification

Excitatory synapses are formed and matured by the cooperative actions of synaptic organizers, such as neurexins (Nrxns), neuroligins (Nlgns), LRRTMs, and Cbln1. Recent super-resolution nanoscopy developments have revealed that many synaptic organizers, as well as glutamate receptors and glutamate release machinery, exist as nanoclusters within synapses. However, it is unclear how such nanodomains interact with each other to organize excitatory synapses invivo. By applying X10 expansion microscopy to epitope tag knockin mice, we found that Cbln1, Nlgn1, and LRRTM1, which share Nrxn as a common presynaptic receptor, form overlapping or separate nanodomains depending on Nrxn with or without a sequence encoded by splice site4. The size and position of glutamate receptor nanodomains of GluD1, NMDA, and AMPA receptors were regulated by Cbln1, Nlgn1, and LRRTM1 nanodomains, respectively. These findings indicate that Nrxns anterogradely regulate the postsynaptic nanoscopic architecture of glutamate receptors through competition and coordination of Nrxn ligands.

Roads to Stat3 Paved with Cadherins.

The engagement of cadherins, cell-to-cell adhesion proteins, triggers a dramatic increase in the levels and activity of the Rac/Cdc42 GTPases, through the inhibition of proteasomal degradation. This leads to an increase in transcription and secretion of IL6 family cytokines, activation of their common receptor, gp130, in an autocrine manner and phosphorylation of the signal transducer and activator of transcription-3 (Stat3) on tyrosine-705 by the Jak kinases. Stat3 subsequently dimerizes, migrates to the nucleus and activates the transcription of genes involved in cell division and survival. The Src oncogene also increases Rac levels, leading to secretion of IL6 family cytokines and gp130 activation, which triggers a Stat3-ptyr705 increase. Interestingly, at the same time, Src downregulates cadherins in a quantitative manner, while cadherins are required to preserve gp130 levels for IL6 family signalling. Therefore, a fine balance between Src527F/Rac/IL6 and Src527F/cadherin/gp130 levels is in existence, which is required for Stat3 activation. This further demonstrates the important role of cadherins in the activation of Stat3, through preservation of gp130 function. Conversely, the absence of cadherin engagement correlates with low Stat3 activity: In sparsely growing cells, both gp130 and Stat3-ptyr705 levels are very low, despite the fact that cSrc is active in the FAK (focal adhesion kinase)/cSrc complex, which further indicates that the engagement of cadherins is important for Stat3 activation, not just their presence. Furthermore, the caveolin-1 protein downregulates Stat3 through binding and sequestration of cadherins to the scaffolding domain of caveolin-1. We hypothesize that the cadherins/Rac/gp130 axis may be a conserved pathway to Stat3 activation in a number of systems. This fact could have significant implications in Stat3 biology, as well as in drug testing and development.

Molecular and Structural Basis of Receptor Binding and Signaling of a Fish Type I IFN with Three Disulfide Bonds.

In mammals, type I IFNs, which commonly contain one or two disulfide bonds, activate the JAK-STAT signaling pathway through binding to the common cell surface receptor formed by IFN-α/β receptor (IFNAR)1 and IFNAR2 subunits. Although type I IFNs are also known to be essential for antiviral defense in teleost fish, very little is known about mechanisms underlying the recognition of fish type I IFNs by associated receptors. In this study, we demonstrate that a type I IFN of large yellow croaker Larimichthys crocea (LcIFNi), belonging to a new subgroup of fish type I IFNs, triggers antiviral response via the conserved JAK-STAT pathway through stable binding with a heterodimeric receptor comprising subunits LcCRFB5 and LcCRFB2. LcIFNi binds to LcCRFB5 with a much higher affinity than to LcCRFB2. Furthermore, we determined the crystal structure of LcIFNi at a 1.39 Å resolution. The high-resolution structure is, to our knowledge, the first reported structure of a type I IFN with three disulfide bonds, all of which were found to be indispensable for folding and stability of LcIFNi. Using structural analysis, mutagenesis, and biochemical assays, we identified key LcIFNi residues involved in receptor interaction and proposed a structural model of LcIFNi bound to the LcCRFB2-LcCRFB5 receptor. The results show that LcIFNi-LcCRFB2 exhibits a similar binding pattern to human IFN-ω-IFNAR2, whereas the binding pattern of LcIFNi-LcCRFB5 is quite different from that of IFN-ω-IFNAR1. Altogether, our findings reveal the structural basis for receptor interaction and signaling of a type I IFN with three disulfide bonds and provide new insights into the mechanisms underlying type I IFN recognition in teleosts.

Metabolic profiles and screening tactics for MDMB-4en-PINACA in human urine and serum samples

MDMB-4en-PINACA (Methyl 3,3-dimethyl-2-[1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido] butanoate) is a potent agonist of the CB1 receptor. In 2021, it was one of the most common synthetic cannabinoid receptor agonists (SCRAs) seized by the Beijing Drug Control Agency. MDMB-4en-PINACA can be hard to detect in biological specimens because of ester hydrolysis. In this work, a highly sensitive liquid chromatography–high-resolution mass spectrometry (LC-HRMS) method was developed for the detection of MDMB-4en-PINACA metabolites in urine, serum, and hair samples. Metabolites from authentic samples were compared with those from human liver microsomes (HLMs) in vitro and in zebrafish in vivo. A total of 75 metabolites, including 44 previously unreported metabolites, were identified from urine samples. We found that 11 metabolic pathways were involved in MDMB-4en-PINACA metabolism, including acetylation, a novel metabolic pathway for SCRAs. Our results revealed that ester hydrolysis and hydroxylation were to the major metabolic pathways involved in MDMB-4en-PINACA metabolism. Using serum samples, we detected 9 metabolites along with the parent drug. Only the parent drug was detected using hair samples. The existence of ADB-4en-PINACA makes the currently used biomarkers for MDMB-4enPINACA not very specific for the intake of MDMB-4en-PINACA. Therefore, based on the identified metabolites and their structural features, we propose more sensitive screening tactics for MDMB-4en-PINACA using urine and serum samples.

Source appointment of potentially toxic elements (PTEs) at an abandoned realgar mine: Combination of multivariate statistical analysis and three common receptor models

Identifying pollution sources and quantifying their contributions are of great importance for proposing management and control strategies of potentially toxic elements (PTEs) in soil. In this study, multivariate statistical analysis and receptor models were combined to identify potential pollution sources and apportion their contributions at an abandoned realgar mine. Principal component analysis (PCA) result shows that three factors are responsible for PTEs, which is also supported by cluster analysis (CA). Correlation analysis and spatial analysis also show that the heavy metals from the same pollution source are of higher correlation coefficients and similar spatial distribution. Three receptor models were combined to apportion contributions of pollution sources. Three pollution sources were detected by absolute principal component analysis-multiple linear regression (APCA-MLR). In contrast, four sources were identified by positive matrix factorization (PMF) and UNMIX. Soil parent material was heavily loaded on Cr, Cu, Ni and Zn, occupying the largest average contribution (30%–43%). Cadmium was mainly derived from agricultural activities with contribution higher than 60%. Arsenic accumulation was mainly associated with mining and smelting activity with contribution higher than 80%. PMF and UNMIX models showed that more than half of Pb concentrations were influenced by industrial activities. Comparatively speaking, APCA-MLR was a well-performing model for all PTEs even though it only detected three pollution sources. The study showed that it was a good choice to apply multiple receptor models in order to achieve more reliable and objective conclusions of source appointment.

Targeting interleukin 4 receptor alpha on tumor-associated macrophages reduces the pro-tumor macrophage phenotype

Tumor-associated macrophages (TAMs) are an abundant tumor-promoting cell type in the tumor microenvironment (TME). Most TAMs exhibit a pro-tumor M2-like phenotype supportive of tumor growth, immune evasion, and metastasis. IL-4 and IL-13 are major cytokines that polarize macrophages to an M2 subset and share a common receptor, IL-4 receptor alpha (IL-4R alpha). Treatment of human ex vivo polarized M2 macrophages and M2 macrophage precursors with IL-4R alpha antagonist antibody Dupilumab (DupixentⓇ) reduces M2 macrophage features, including a shift in cell surface marker protein expression and gene expression. In animal models of prostate cancer, both pharmacologic inhibition of IL-4R alpha and genetic deletion of IL-4R alpha utilizing an Il4ra -/- mouse model result in decreased CD206 on TAMs. These data support IL-4R alpha as a target to reduce the pro-tumor, M2-like macrophage phenotype as a novel adjunct cancer therapy.

PPARα: A potential therapeutic target of cholestasis.

The accumulation of bile acids in the liver leads to the development of cholestasis and hepatocyte injury. Nuclear receptors control the synthesis and transport of bile acids in the liver. Among them, the farnesoid X receptor (FXR) is the most common receptor studied in treating cholestasis. The activation of this receptor can reduce the amount of bile acid synthesis and decrease the bile acid content in the liver, alleviating cholestasis. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) have a FXR excitatory effect, but the unresponsiveness of some patients and the side effect of pruritus seriously affect the results of UDCA or OCA treatment. The activator of peroxisome proliferator-activated receptor alpha (PPARα) has emerged as a new target for controlling the synthesis and transport of bile acids during cholestasis. Moreover, the anti-inflammatory effect of PPARα can effectively reduce cholestatic liver injury, thereby improving patients’ physiological status. Here, we will focus on the function of PPARα and its involvement in the regulation of bile acid transport and metabolism. In addition, the anti-inflammatory effects of PPARα will be discussed in some detail. Finally, we will discuss the application of PPARα agonists for cholestatic liver disorders.

Acquired Resistance to Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer: How Do We Overcome It?

Osimertinib is currently the preferred first-line therapy in patients with non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutation and the standard second-line therapy in T790M-positive patients in progression to previous EGFR tyrosine kinase inhibitor. Osimertinib is a highly effective treatment that shows a high response rate and long-lasting disease control. However, a resistance to the treatment inevitably develops among patients. Understanding the secondary mechanisms of resistance and the possible therapeutic options available is crucial to define the best management of patients in progression to osimertinib. We provide a comprehensive review of the emerging molecular resistance mechanism in EGFR-mutated NSCLC pre-treated with osimertinib and its future treatment applications.

Integration of light and temperature sensing by liquid-liquid phase separation of phytochrome B

Light and temperature in plants are perceived by a common receptor, phytochrome B (phyB). How phyB distinguishes these signals remains elusive. Here, we report that phyB spontaneously undergoes phase separation to assemble liquid-like droplets. This capacity is driven by its C terminus through self-association, whereas the intrinsically disordered N-terminal extension (NTE) functions as a biophysical modulator of phase separation. Light exposure triggers a conformational change to subsequently alter phyB condensate assembly, while temperature sensation is directly mediated by the NTE to modulate the phase behavior of phyB droplets. Multiple signaling components are selectively incorporated into phyB droplets to form concentrated microreactors, allowing switch-like control of phyB signaling activity through phase transitions. Therefore, light and temperature cues are separately read out by phyB via allosteric changes and spontaneous phase separation, respectively. We provide a conceptual framework showing how the distinct but highly correlated physical signals are interpreted and sorted by one receptor.