Integration of signal transduction pathways in sensory epithelial enteroendocrine cells

作者：Shreya S. Bellampalli, Vikram Joshi, Gennadiy Fonar, Arthur Beyder · 发表于：Molecular Biology of the Cell · 年份：2025 · DOI：10.1091/mbc.e24-03-0143 · 被引用次数：3 · 研究领域：Pancreatic function and diabetes、Adenosine and Purinergic Signaling、Receptor Mechanisms and Signaling

The gastrointestinal (GI) tract plays a crucial role in nutrient absorption, motility, and metabolism, while serving as a barrier against pathogens. The intestinal epithelial layer, particularly enteroendocrine cells (EEC), is pivotal in sensing luminal stimuli due to its strategic position. Although comprising only 1% of the GI epithelium, in total EEC comprises perhaps the largest endocrine organ that couples GI luminal stimuli with release of hormones and neurotransmitters such as serotonin, glucagon-like peptide-1 (GLP-1), and peptide-tyrosine-tyrosine (PYY), which regulate local and systemic physiology. In this review, we use EECs as a model to explore critical intracellular signaling pathways-centering around calcium (Ca²⁺) and cyclic adenosine monophosphate (cAMP). EECs utilize ionotropic and metabotropic receptors to detect luminal stimuli, leading to increased intracellular cytoplasmic Ca²⁺ and altered intracellular cAMP dynamics. Ca²⁺ influx is critical for the exocytosis of signaling molecules. The interplay between Ca²⁺ and cAMP signaling pathways enhances the release of these molecules, affecting both local and systemic responses. We make a point to discuss the conventional and emerging methodologies for measuring Ca²⁺ and cAMP dynamics in EECs, which is a rapidly expanding toolbox, containing genetically encoded indicators and resonance energy transfer techniques. Understanding these signaling cascades is essential for deciphering the complex roles of EECs in GI...