Biology subjects

Choi, I.

Publications and source records attributed to Choi, I..

At least 19 recordsLinked to original sources

bioRxiv2026

Auditory Working Memory and Sound Segregation Ability Predict Speech-in-Noise in Adult Cochlear Implant Users

ObjectivesOutcomes following cochlear implantation vary substantially across adult recipients, and the cognitive and perceptual factors contributing to this variability are not fully understood. This poses a challenge for developing strategies to improve cochlear implant outcomes, as such approaches require a clearer understanding of the mechanisms underlying individual listening difficulties. In this study, we investigated auditory cognitive measures in cochlear implant (CI) users to further elucidate the origins of this variability. DesignThirty-seven adult cochlear implant users completed measures of auditory cognition, comprising auditory working memory (AWM) and sound segregation ability, measured using an auditory figure-ground task (AFG), as well as measures of peripheral temporal and spectral processing, comprising the temporal modulation detection threshold (TMDT) and spectral ripple discrimination threshold (SRDT). Speech perception outcomes were assessed using word-in-noise (WIN) and sentence-in-noise (SIN) tasks. Separate multiple linear regression models evaluated the unique contribution of the auditory cognition measures to WIN and SIN performance, after accounting for the peripheral measures. ResultsBoth regression models explained a substantial proportion of variance in speech-in-noise outcomes (WIN: adjusted R{superscript 2} = 0.55; SIN: adjusted R{superscript 2}=0.57, both p < 0.001). For WIN performance, AFG and AWM were significant predictors. A similar pattern was found for SIN performance, where lower AWM ability and poorer AFG segregation were linked to poorer sentence listening in noise. No significant effects of spectral ripple discrimination or temporal modulation detection were observed in either model, even though both were significantly correlated with WIN performance. ConclusionsThese findings indicate that auditory working memory and sound segregation ability are robust predictors of speech-in-noise outcomes in adult cochlear implant users, across both word- and sentence-level measures. Together, the results may help explain why speech-in-noise outcomes remain highly variable among CI users, even when basic sensory encoding abilities are taken into account. Incorporating measures of auditory working memory and fundamental sound segregation may therefore improve outcome prediction and help in developing more individualised rehabilitation strategies.

neuroscience↗

bioRxiv2026

Notch signaling in the embryonic ectoderm promotes periderm cell fate and represses mineralization of vibrissa hair follicles

The Notch signaling pathway is a critical means to regulate cell fate choice in animals. Appropriate regulation of this pathway is also required for human face formation as both loss and gain of function mutations of Notch signaling can cause syndromes with craniofacial abnormalities. Here we examine the consequences of manipulation of Notch signaling in the early mouse embryonic ectoderm by either removing the transcriptional effector Rbpj or expressing a constitutively active form of the Notch1 intracellular domain. Loss of Rbpj resulted in cleft secondary palate but strikingly was also associated with the ectopic mineralization of vibrissa follicles. In contrast, activation of Notch signaling resulted in multiple embryonic defects including a fully penetrant bilateral cleft lip and palate. Further, single cell RNA-seq data indicated a switch from a basal epithelial cell identity towards periderm when Notch signal transduction was elevated. These cell fate changes were accompanied by misregulation of genes and pathways known to impact human and mouse orofacial clefting including Grhl3, Irf6, and Wnt pathway. Together, these findings provide insight into human craniofacial conditions caused by misregulated Notch activity. SUMMARY STATEMENTOur studies demonstrate that Notch signaling in the embryonic ectoderm stimulates periderm cell fate while also repressing transformation of the inner root sheath of whisker follicles into mineralized tissue.

developmental biology↗

bioRxiv2025

Rapid discovery of antiviral targets through dimensionality reduction of genome-scale metabolic models

The COVID-19 pandemic underscored the urgent need for rapid and broadly applicable strategies to identify antiviral targets against emerging pathogens. Conventional approaches, which rely on detailed viral characterization and large-scale drug screening, are too slow to address this challenge. Here, we introduce a transcriptome-based computational framework that integrates genome-scale metabolic models with dimensionality reduction to uncover host metabolic vulnerabilities that support viral replication. Applying this approach to bulk and single-cell RNA-seq data from HCoV-OC43-infected cells and organoids identified oxidative phosphorylation as a key vulnerability, and pharmacological inhibition of complex I effectively curtailed viral replication. Extending the framework to SARS-CoV-2 and MERS-CoV revealed pyrimidine catabolism as a conserved antiviral pathway, with inhibition of its rate-limiting enzyme DPYD suppressing replication in organoid models. Re-analysis of SARS-CoV-2 patient metabolome data further confirmed elevated DPYD activity, underscoring its clinical relevance. Together, these findings establish a generalizable and rapid strategy for host-directed antiviral discovery, providing a foundation for precision therapeutics and pandemic preparedness. Significance StatementHost-directed antiviral therapies offer several advantages in antiviral research, but identifying key host factors poses a significant challenge. By integrating genome-scale metabolic models with single-gene knockout simulation and dimensionality reduction, we developed a computational framework based on single and bulk RNA-seq data that can systematically pinpoint host pathways whose downregulation is predicted to rewire virus-induced metabolic alterations. Applying this approach to multiple human coronaviruses reveals unique metabolic vulnerabilities, and we experimentally demonstrate that inhibiting these host metabolic pathways reduces viral replication. This framework provides a generalizable antiviral strategy to discern effective targets and can be further extended to investigate virus-host metabolic interactions.

systems biology↗

bioRxiv2025

β-arrestin recruitment facilitates a direct association with G proteins

G protein-coupled receptors (GPCRs) are targets for almost a third of all FDA-approved drugs. GPCRs are known to signal through both heterotrimeric G proteins and {beta}-arrestins. Traditionally these pathways were viewed as largely separable, with G proteins primarily initiating downstream signaling while {beta}-arrestins modulate receptor trafficking and desensitization in addition to regulating their own signaling events. Recent studies suggest an integrated role of G proteins and {beta}-arrestins in GPCR signaling, however the cellular and biochemical requirements for G protein: {beta}-arrestin interactions remain unclear. Here we show that G proteins and {beta}-arrestins can directly interact. Through utilization of {beta}-arrestin-biased receptors and artificially enforced {beta}-arrestin relocalization, we demonstrate that recruitment of {beta}-arrestin to the plasma membrane is sufficient to interact with the G protein Gi. Using purified proteins, we show that Gi directly interacts with {beta}-arrestin. In addition, we find that Gi family members differ in their degree of association with {beta}-arrestin, and that a large degree of this selectivity resides within the alpha helical domain of Gi. These findings delineate the cellular and biochemical conditions that drive direct interactions between G proteins and {beta}-arrestins and illuminate the molecular basis for how they work together to effect GPCR signaling.

biochemistry↗

bioRxiv2025

Serine auxotrophy is a targetable vulnerability driven by PSAT1 suppression in AML

Serine metabolism is of growing biologic and therapeutic interest in cancer. Upregulation of the serine synthesis pathway (SSP) can fuel tumor growth, and cancers with this phenotype are often sensitive to SSP inhibitors. In parallel, dietary restriction of serine and glycine (SG) can suppress some cancers, but the determinants of sensitivity to this approach are poorly understood. This is especially true in acute myeloid leukemia (AML), where serine metabolism has been less explored. We report that a subset of human AML cell lines and primary samples are completely dependent on external serine, known as serine auxotrophy. These leukemias consistently suppressed the SSP enzyme PSAT1, failed to synthesize serine, responded to SG restriction in vivo, and were rescued by restoring PSAT1. We also found that AML with an SF3B1 K700E mutation showed additional dependence on the SSP enzyme PHGDH, that SG restriction synergized with venetoclax in serine auxotrophic AML, and that MECOM rearrangement was strongly associated with PSAT1 suppression and serine auxotrophy. These findings define a metabolically distinct AML subtype and nominate it for targeting by SG restriction.

cancer biology↗

bioRxiv2025

Novel transcription factor BTNL9 enhances tumor suppression and drug sensitivity in non-small cell lung cancer through cell cycle regulation

BackgroundButyrophilins (BTNs) are immunoglobulin superfamily proteins involved in immune regulation. Among them, BTNL9 has unique structural features, including a bZIP-like domain, suggesting a potential transcriptional role. While BTNL9 is known to suppress T cell activation, its function in cancer remains largely unexplored. Recent studies suggest it may inhibit tumor progression and correlate with improved prognosis in multiple cancers. However, its molecular mechanisms and regulatory impact on lung cancer remain unclear. This study investigates the role of BTNL9 as a transcription factor and its implications for tumor progression and therapy. MethodsChIP-seq identified BTNL9-binding sites, followed by RNA-seq to assess transcriptomic profiles and validated by western blot. Drug sensitivity was evaluated through cytotoxicity assays. A xenograft model was applied to assess the effect of BTNL9 on tumor growth. TCGA data analysis examined correlations with survival, cell cycle regulators, and immune infiltration. ResultsChIP-seq identified 26,610 BTNL9 binding peaks, mapping to 9,707 genes near transcription start sites. RNA-seq and western blotting showed BTNL9 regulates cell cycle (E2F1, CDKN1A, CDK1, CDC25C, FOXM1), DNA replication (MCM2/3/7, ORC6), and p53-related transcription (BBC3, GADD45A). Integrative analysis found that 74.8% of differentially expressed genes were directly regulated by BTNL9. Functionally, BTNL9 overexpression induced cell cycle arrest, reduced proliferation, and suppressed tumor growth in vivo. BTNL9 enhanced bortezomib sensitivity in both A549 and NCI-H460 cells, with etoposide effects being more pronounced in A549. Higher BTNL9 levels strongly suppressed the expression of FOXM1, CDC25C, CDK1, CDK2, CCNA2 and CCNB1 and negatively correlated with these markers in LUAD TCGA data. Elevated BTNL9 expression was associated with improved survival, complete remission, and increased immune infiltration, including macrophages, CD8+ T cells, NK cells, and B cells in cancer tissues. ConclusionsBTNL9 functions as a transcription factor, suppresses tumor growth, and enhances drug sensitivity. Its correlation with survival and immune infiltration suggests potential role as a tumor suppressor and predictive biomarker for chemotherapy response.

cancer biology↗

bioRxiv2025

rTCT: Rodent Triangle Completion Task to facilitate translational study of path integration

Path integration is navigation in the absence of environmental landmarks and is a primary cognitive mechanism underlying spatial memory. Path integration performance is primarily assessed in humans using the Triangle Completion Task (TCT). In humans, TCT has shown promise for the early diagnosis of Alzheimers disease. In rodents, however, path integration is assessed using a wide variety of tasks but none of which currently provide a homologue for the TCT. As rodents are routinely used as preclinical models, homologous path integration tasks that result in comparable performance metrics between species are important. In the present study we developed and tested a novel rodent version of the triangle completion task to enhance cross species comparability of path integration performance. Rats were able to comprehend and perform the task. A group of Alzheimers disease model rats (TgF344-AD) exhibited similar path integration performance to their wild-type littermates; however, analysis of behavioural structure suggests use of differing behavioural strategies. This work establishes a novel rodent homologue of the triangle completion task, facilitating enhanced reverse translational study of human path integration.

neuroscience↗

bioRxiv2025

Phosphorus Availability Modulates Flowering Time Through Subcellular Reprogramming of bGLU25 and GRP7 in Flowering Plants

The transition from vegetative to reproductive growth is vital for plant fitness and crop yield and is strongly influenced by nutrient availability. While nitrogen deficiency accelerates flowering, phosphorus (P) limitation delays it. However, the molecular basis for how P availability regulates flowering time remains unclear. Here, through genome-wide association mapping in Arabidopsis, we uncover genetic variation in {beta}-GLUCOSIDASE 25 (bGLU25) that modulates flowering under P-limited conditions. In P-sufficient environments, bGLU25 localizes to the endoplasmic reticulum. Under P limitation, however, bGLU25 translocates to the cytosol, a process mediated by P-regulated SERINE CARBOXY PEPTIDASE 50 (SCP50). In the cytosol, bGLU25 binds to JACALIN-LECTIN LIKE1 (AtJAC1), preventing the nuclear translocation of the Flowering Locus C (FLC) regulator GLYCINE-RICH RNA-BINDING PROTEIN 7 (GRP7). This cytosolic sequestration of GRP7 under P-deprivation elevates FLC expression, delaying flowering. Moreover, in the monocot rice, the homologs of bGLU25 also modulate flowering responses to P availability, indicating a conserved role for bGLU25 across flowering plants. Our findings provide a molecular framework for breeding strategies aimed at optimizing flowering time in response to P levels.

plant biology↗

bioRxiv2024

Latent encoding of movement in primary visual cortex

Neurons in the primary visual cortex (V1) are classically thought to encode spatial features of visual stimuli through simple population codes: each neuron exhibits a preferred orientation and preferred spatial frequency, both of which remaining invariant to other aspects of the visual stimulus. Here, we show that this simple rule does not apply to the representation of major features of stimulus motion, including stimulus direction and temporal frequency (TF). We collected an extensive dataset of cat (of either sex) V1 responses to stimuli covarying in orientation, direction, spatial frequency, and TF to assess the extent of motion selectivity. We show that preferred TF is mostly uniform across the cortical surface. Yet, in over half of V1, the preferred direction is reversed with changing stimulus TF, revealing four distinct map motifs embedded in V1s functional architecture. Similarly, despite the lack of spatial modulation for the preferred TF map and the lack of invariance for the preferred direction map, we found using convolutional neural networks that direction, TF and stimulus speed can be accurately decoded from V1 responses at all cortical locations. These findings suggest that subtle modulations of V1 activity may convey fine information about stimulus motion, pointing to a novel primary sensory encoding mechanism despite complex co-variation of responses to multiple attributes across V1 neurons. Significance StatementUnderstanding how the external world is represented in the brain has long been a central endeavor in neuroscience. In the mammalian primary visual cortex (V1), groups of neurons encode stimulus properties through changes in activity, with "preferred" stimuli eliciting maximal responses, as demonstrated for orientation and spatial frequency. Using an extensive dataset of neuronal responses, we investigated whether V1 also encodes motion speed. We found that cortical response organization remains largely invariant, with neurons exhibiting a uniform preference for temporal frequency. Yet, machine learning algorithms decode motion speed with remarkable precision, revealing that subtle, spatially distributed modulations of activity underlie speed encoding. Moreover, we show that preferred direction flips with speed across 80% of cortex, uncovering a novel co-organization of motion and direction information in V1.

neuroscience↗

bioRxiv2024

British Version of the Iowa Test of Consonant Perception

The Iowa Test of Consonant Perception (ITCP) is a single-word closed-set speech- in-noise test with well-balanced phonetic features that provides a reliable testing option for real-world listening. Objectives. The current study aimed to establish a UK version of the test (B-ITCP) based on the British received pronunciation. Design. We conducted a validity test with 46 participants using the B-ITCP test, a sentence-in- noise test, and audiogram. Results. The B-ITCP demonstrated excellent test-retest reliability, cross-talker validity, and good convergent validity, consistent with the US results. Conclusions. These findings suggest that B-ITCP is a reliable measure of speech-in-noise perception, to facilitate comparative or combined studies in USA and UK. All materials (application and scripts) to run or construct the B-ITCP and ITCP are freely available online.

neuroscience↗

bioRxiv2024

RAB12-LRRK2 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes

Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and the phosphorylation levels are elevated by Parkinsons disease (PD)-linked mutations of LRRK2. However, the precise function of the specific RAB GTPase targeted by LRRK2 signaling in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brains through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis. Mechanistically, RAB12 cooperates with LRRK2 to inhibit primary ciliogenesis and regulate centrosome homeostasis in astrocytes through enhancing the phosphorylation of RAB10 and recruiting Rab interacting lysosomal protein like 1 (RILPL1), while the functions of RAB12 require a direct interaction with LRRK2 and LRRK2 kinase activity. Furthermore, the ciliary deficits and centrosome alteration caused by the PD-linked LRRK2-G2019S mutation are prevented by the deletion of Rab12 in astrocytes. Thus, our study reveals a physiological function of the RAB12-LRRK2 complex in regulating ciliogenesis and centrosome homeostasis. The RAB12-LRRK2 structure offers a guidance in the therapeutic development of PD by targeting the RAB12-LRRK2 interaction.

neuroscience↗

bioRxiv2024

MDRepo - an open environment for data warehousing and knowledge discovery from molecular dynamics simulations

BackgroundMolecular Dynamics (MD) simulation of biomolecules provides important insights into conformational changes and dynamic behavior, revealing critical information about folding and interactions with other molecules. This enables advances in drug discovery and the design of therapeutic interventions. The collection of simulations stored in computers across the world holds immense potential to serve as training data for future Machine Learning models that will transform the prediction of structure, dynamics, drug interactions, and more. A needIdeally, there should exist an open access repository that enables scientists to submit and store their MD simulations of proteins and protein-drug interactions, and to find, retrieve, analyze, and visualize simulations produced by others. However, despite the ubiquity of MD simulation in structural biology, no such repository exists; as a result, simulations are instead stored in scattered locations without uniform metadata or access protocols. A solutionHere, we introduce MDRepo, a robust infrastructure that supports a relatively simple process for standardized community contribution of simulations, activates common downstream analyses on stored data, and enables search, retrieval, and visualization of contributed data. MDRepo is built on top of the open-source CyVerse research cyberinfrastructure, and is capable of storing petabytes of simulations, while providing high bandwidth upload and download capabilities and laying a foundation for cloud-based access to its stored data.

biochemistry↗

bioRxiv2024

Locomotion-dependent auditory gating to the parietal cortex mediates flexible multisensory decisions

Decision-making in mammals fundamentally relies on integrating multiple sensory inputs, with conflicting information resolved flexibly based on a dominant sensory modality. However, the neural mechanisms underlying state-dependent changes in sensory dominance remain poorly understood. Our study demonstrates that locomotion in mice shifts auditory-dominant decisions toward visual dominance during audiovisual conflicts. Using circuit-specific calcium imaging and optogenetic manipulations, we found that weakened visual representation in the posterior parietal cortex (PPC) leads to auditory-dominant decisions in stationary mice. Prolonged locomotion, however, promotes visual dominance by inhibiting auditory cortical neurons projecting to the PPC (ACPPC). This shift is mediated by secondary motor cortical neurons projecting to the auditory cortex (M2AC), which specifically inhibit ACPPC neurons without affecting auditory cortical projections to the striatum (ACSTR). Our findings reveal the neural circuit mechanisms underlying auditory gating to the association cortex depending on locomotion states, providing insights into the state-dependent changes in sensory dominance during multisensory decision-making.

animal behavior and cognition↗

bioRxiv2023

Effects of Alternative Splicing-Specific Knockdown of Tjp1 α+ by Rbm47 on Tight Junctions Assembly during Blastocyst Development

Tjp1 + is considered a crucial protein involved in the stepwise assembly of tight junctions (TJs) between compaction and blastocoel cavitation in early development. In this study, we investigated the specific role of Tjp1 + in TJ formation by employing an alternative splicing-specific knockdown of the Tjp1 + exon. To deplete Tjp1 + expression, we used siRNA targeting RNA-binding protein 47 (Rbm47), which induces the inclusion of the + exon in Tjp1 mRNA. The knockdown resulted in approximately 85% reduction in Rbm47 mRNA levels and 75% reduction in Tjp1 + mRNA levels in blastocysts. Surprisingly, despite this knockdown, blastocyst development and TJ permeability of trophectoderm were unaffected. Additionally, we observed an interaction between Tjp1 - and Ocln in Rbm47 knockdown blastocysts, suggesting a compensatory role of Tjp1 -. Overall, our findings indicate that Tjp1 + is not essential for the stepwise assembly of TJs and the completion of TJ biogenesis during blastocyst development in mice although a minimal amount of remaining Tjp1 + is sufficient for TJs assembly. Summary statementSelective loss of Tjp1 + mediated by Rbm47 knockdown did affect mouse blastocyst development, suggesting that Tjp1 + may not be crucial for stepwise TJs assembly during blastocyst development

cell biology↗

bioRxiv2023

CyVerse: Cyberinfrastructure for Open Science

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 110,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in two countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.

scientific communication and education↗

bioRxiv2023

Phosphorylation barcodes direct biased chemokine signaling at CXCR3

G protein-coupled receptor (GPCR) biased agonism, the activation of some signaling pathways over others, is thought to largely be due to differential receptor phosphorylation, or "phosphorylation barcodes." At chemokine receptors, ligands act as "biased agonists" with complex signaling profiles, which contributes to the limited success in pharmacologically targeting these receptors. Here, mass spectrometry-based global phosphoproteomics revealed that CXCR3 chemokines generate different phosphorylation barcodes associated with differential transducer activation. Chemokine stimulation resulted in distinct changes throughout the kinome in global phosphoproteomic studies. Mutation of CXCR3 phosphosites altered {beta}-arrestin conformation in cellular assays and was confirmed by molecular dynamics simulations. T cells expressing phosphorylation-deficient CXCR3 mutants resulted in agonist- and receptor-specific chemotactic profiles. Our results demonstrate that CXCR3 chemokines are non-redundant and act as biased agonists through differential encoding of phosphorylation barcodes and lead to distinct physiological processes.

biochemistry↗

bioRxiv2022

Three consecutive glycolysis enzymes are involved in autophagic flux regulation through monitoring nutrient availability

Autophagy serves as an important recycling route for growth and survival of eukaryotic organisms in nutrient-deficient conditions. When confronted with starvation, metabolic flux is coordinated by individual metabolic enzymes. Given that the metabolic diversity of carbon in eukaryotes is related to their lifestyle, autophagy may be modulated by metabolic enzymes by monitoring carbon flux. Here, we attempted to identify carbon metabolic genes that modulate autophagy using VIGS screening of 45 glycolysis- and the Calvin-Benson cycle-related genes. We report here that three consecutive triose-phosphate-processing enzymes involved in the cytosolic glycolysis, TPI (triose-phosphate-isomerase), GAPC (glyceraldehyde-3-phosphate dehydrogenase), and PGK (phosphoglycerate kinase), designated TGP, negatively regulate autophagy. Depletion of TGP enzymes result in spontaneous autophagy induction and increases ATG1 kinase activity. TGP enzymes interact with ATG101, a regulatory component of the ATG1 kinase complex. Spontaneous autophagy induction and abnormal growth under insufficient sugar in the TGP mutants is suppressed by crossing with the atg101 mutant. Considering that triose-phosphates are photosynthates transported to the cytosol from active chloroplasts, the TGP enzymes may be strategically positioned to monitor the flow of photosynthetic sugars and modulate autophagy accordingly. Collectively, these results suggest that TGP enzymes negatively control autophagy acting upstream of the ATG1 complex, which is critical for seedling development.

plant biology↗

bioRxiv2022

Subcellular localization of GPCR kinases differentially modulate biased signaling at CXCR3

Some G protein-coupled receptors (GPCRs) demonstrate biased signaling, where ligands of the same receptor differentially activate specific downstream signaling pathways over others. Ligand-specific receptor phosphorylation by GPCR kinases (GRKs) is one mechanism underlying this phenomenon. Recent evidence demonstrates that GPCRs traffic to and signal from subcellular compartments beyond the plasma membrane, a paradigm termed location bias. Here, we show that GRKs translocate to endosomes following stimulation of the chemokine receptor CXCR3 and other GPCRs. The GRK recruitment patterns at the plasma membrane and endosome are distinct and depend on the identity of the ligand used to activate the receptor. Using cells deficient of GRKs, we demonstrate that biased ligands have unique signaling profiles upon rescue of location-specific GRK isoforms. Our work highlights a role of the GRKs in location-biased GPCR signaling and demonstrates the complex interactions between ligand, GRK isoform and cellular location that contribute to biased signaling.

biochemistry↗