Publications HAL de Yvinec

2021

titre
β-arrestins and endocrine-related GPCRs
article
Cellular Endocrinology in Health and Disease, Elsevier, pp.445-458, 2021, 978-0-12-819801-8. ⟨10.1016/B978-0-12-819801-8.00021-1⟩
resume
G protein-coupled receptors (GPCRs) allow target cells to respond to a wide array of hormones. Mounting evidences point to GPCRs being functionally coupled to multiple transduction mechanisms, some of them not involving heterotrimeric G proteins. Among these emerging mechanisms, it has been well established that β-arrestins recruited to active GPCRs control not only their desensitization and internalization, but also assemble and activate signaling modules in different intracellular compartments. Importantly, β-arrestin-dependent transduction applies to most GPCRs, including those involved in endocrine mechanisms. This concept, in conjunction with remarkable advances made over the last decade in structural biology and biophysics of GPCRs, supports the notion of ligand-selective signaling also known as pharmacological bias. In this chapter, we review the role of β-arrestin recruitment in the signaling and trafficking of endocrine-related GPCRs. We also focus on biased ligands capable of selectively activating intracellular pathways downstream of endocrine-related GPCRs and discuss their potential therapeutic applications.
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titre
The follicle-stimulating hormone signaling network in gonadal cells.
article
Alfredo Ulloa-Aguirre; Ya-Xiong Tao. Cellular endocrinology in health and disease, Second Edition, Academic Press, 486 p., 2021, 9780128198018. ⟨10.1016/B978-0-12-819801-8.00020-X⟩
resume
FSH (follicle-stimulating hormone) is a master endocrine regulator of somatic cells of the gonads that support gametogenesis. In the male, FSH dictates the Sertoli cell proliferation rate prior to puberty, then maintains their main biological roles as nurturing cells and physical support to spermatogenesis throughout life. In the female, FSH is instrumental in processing the terminal differentiation phase of folliculogenesis that progressively drives the ovarian follicle to ovulation. The biological function of FSH is transduced by a membrane receptor, the FSH receptor (FSHR). Deciphering the molecular bases of the developmental switch in FSH biological activities is required to gain insights into FSH-induced signaling pathways. This quest has led to the identification of a complex interconnected signaling network affected by testicular paracrine factors, implying not only protein post-translational modifications but also regulation by microRNA and chromatin remodeling. In the female, the emphasis is now placed on deciphering the complex functional relationships between the LHCGR (luteinizing hormone/choriogonadotropin hormone receptor) and the FSHR that trigger intertwined signaling networks in the same granulosa cell type. Breakthroughs in the organization and dynamic functioning of the FSH-induced signaling network are expected to identifying novel regulatory processes and therapeutic strategies for infertilities and contraception.
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2019

titre
Workflow description to dynamically model beta-arrestin signaling networks
article
Beta-arrestins- Methods and protocols, 1957, , 2019, Methods in Molecular Biology, ⟨10.1007/978-1-4939-9158-7_13⟩
resume
Dynamic models of signaling networks allow the formulation of hypotheses on the topology and kinetic rate laws characterizing a given molecular network, in-depth exploration and confrontation with kinetic biological data. Despite its standardization, dynamic modeling of signaling networks still requires successive technical steps that need to be carefully performed. Here, we detail these steps by going through the mathematical and statistical framework. We explain how it can be applied to the understanding of β-arrestin-dependent signaling networks. We illustrate our methodology through the modeling of β-arrestin recruitment kinetics at the Follicle Stimulating Hormone (FSH) receptor supported by in-house Bioluminescence Resonance Energy Transfer (BRET) data.
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https://hal.science/hal-02374486/file/Yvinec2019.pdf BibTex

2018

titre
Follicle-stimulating hormone receptor: Advances and remaining challenges
article
G protein-coupled receptors: emerging paradigms in activation, signaling and regulation- Part A, 338 (1ère ed.), Elsevier, pp.1-58, 2018, International Review of Cell and Molecular Biology, 978-0-12-813772-7. ⟨10.1016/bs.ircmb.2018.02.001⟩
resume
Follicle-stimulating hormone (FSH) is produced in the pituitary and is essential for reproduction. It specifically binds to a membrane receptor (FSHR) expressed in somatic cells of the gonads. The FSH/FSHR system presents many peculiarities compared to classical G protein-coupled receptors (GPCRs). FSH is a large naturally heterogeneous heterodimeric glycoprotein. The FSHR is characterized by a very large NH2-terminal extracellular domain, which binds FSH and participates to the activation/inactivation switch of the receptor. Once activated, the FSHR couples to Gαs and, in some instances, to other Gα-subunits. GPCR kinases and β-arrestins are also recruited to the FSHR and account for its desensitization, the control of its trafficking and its intracellular signaling. Of note, the FSHR internalization and recycling are very fast and involve very early endosomes (EE) instead of EE. All the transduction mechanisms triggered upon FSH stimulation lead to the activation of a complex signaling network that controls gene expression by acting at multiple levels. The integration of these mechanisms not only leads to context-adapted responses from the target gonadal cells but also indirectly affects the fate of germ cells. Depending on the physiological/developmental stage, FSH elicits proliferation, differentiation, or apoptosis in order to maintain the homeostasis of the reproductive system. Pharmacological tools targeting FSHR recently came to the fore and open promising prospects both for basic research and therapeutic applications. This chapter provides an updated review of the most salient aspects and peculiarities of FSHR biology and pharmacology.
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https://hal.science/hal-02373607/file/De%20Pascali%20et%20al_manuscript.pdf BibTex

2016

titre
Deterministic and stochastic Becker-Döring equations: Past and recent mathematical developments
article
Stochastic Processes, Multiscale Modeling, and Numerical Methods for Computational Cellular Biology, Editions Springer, pp.175-204, 2016, ⟨10.1007/978-3-319-62627-7⟩
resume
We present a survey on the results on a particular coagulation-fragmentation model given by the Becker-D\"oring equations. For both the deterministic and stochastic versions, we include well-posedness, long-time behavior, convergence rate towards equilibrium, coarsening and relation to transport equations, time-dependent properties, metastability and classical nucleation theory. All along this survey, we highlight recent results and open questions.
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https://hal.science/hal-01512134/file/survey-bd-vfinal_reviewed.pdf BibTex