Abstract
Models of G protein-coupled receptor (GPCR) signaling have dramatically altered over the past two decades. Indeed, GPCRs such as the follicle-stimulating hormone receptor (FSHR) have contributed to these new emerging models. We now understand that receptor signaling is highly organized at a spatial level, whereby signaling not only occurs from the plasma membrane but distinct intracellular compartments. Recent studies in the role of membrane trafficking and spatial organization of GPCR signaling in regulating gonadotropin hormone receptor activity has identified novel intracellular compartments, which are tightly linked with receptor signaling and reciprocally regulated by the cellular trafficking machinery. Understanding the impact of these cell biological mechanisms to physiology and pathophysiology is emerging for certain GPCRs. However, for FSHR, the potential impact in both health and disease and the therapeutic possibilities of these newly identified systems is currently unknown, but offers the potential to reassess prior strategies, or unveil novel opportunities, in targeting this receptor.
Highlights
The follicle-stimulating hormone receptor (FSHR) belongs to the superfamily of G proteincoupled receptors (GPCRs)
We understand the signaling pathways activated by GPCRs are much more complex to mediate the many distinct functions these receptors play in all physiological systems, and important to decipher is how such signal pathways are regulated
This review will discuss our current understanding of the molecular mechanisms and signaling roles of membrane trafficking of FSHR, and how gonadotropin hormone receptors have shed light on novel cell biological pathways potentially applicable to many GPCRs
Summary
The follicle-stimulating hormone receptor (FSHR) belongs to the superfamily of G proteincoupled receptors (GPCRs). We understand the signaling pathways activated by GPCRs are much more complex to mediate the many distinct functions these receptors play in all physiological systems, and important to decipher is how such signal pathways are regulated. These novel mechanisms are beginning to open up new avenues for therapeutic exploitation. This review will discuss our current understanding of the molecular mechanisms and signaling roles of membrane trafficking of FSHR, and how gonadotropin hormone receptors have shed light on novel cell biological pathways potentially applicable to many GPCRs. We will primarily focus on postendocytic intracellular trafficking, and discuss how this novel cell biology could shed light on specific facets of FSH/FSHR function and its implications to endocrine function
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