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To determine whether caveolae and caveolin-1 affect the distribution of calcitonin receptor-like receptors (CLR) in vascular smooth muscle cell (VSMC) membranes, we have used VSMCs cell line A10. We found that calcitonin gene-related peptide (CGRP) reduced CLR protein in the VSMC membrane in a time-dependent manner, which was dramatically decreased after 4 h CGRP treatment, and remained at a low level after 16 h. CGRP8-37 or β-cyclodextrin (β-CD) blocked this effect, without changing the total levels of CLR protein and mRNA in the cells. Co-immunoprecipitation experiments showed that CLR bound to caveolin-1 in cell membrane fractions. Confocal laser microscopic studies confirmed this co-localization relationship at the cell plasma membrane. Thus, our data indicate that the structural integrity of caveolae plays an important role in regulating subcellular distribution of CLR.
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http://dx.doi.org/10.1139/bcb-2013-0020 | DOI Listing |
Int J Biol Macromol
September 2025
Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Tabriz USERN Office, Universal Scientific Education and Research Network (USERN), Tabriz, Iran.
Calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein type 1 (RAMP1) are key components of the calcitonin gene-related peptide (CGRP) receptor, which is upregulated during migraine attacks, contributing to enhanced CGRP signaling. This study aimed to investigate the binding of covalent organic framework (COFs) models to CLR/RAMP1 at the molecular level using molecular dynamics (MD) and docking simulations. To assess the efficacy and inhibitory effects of COF structures on the CLR/RAMP1 complex, two antimigraine drugs, ubrogepant and rimegepant, were used as controls.
View Article and Find Full Text PDFNat Immunol
September 2025
Jill Roberts Institute for Research in Inflammatory Bowel Disease, New York, NY, USA.
Neuro-immune circuits regulate innate and adaptive immunity at barrier surfaces. However, the differential impact of these circuits on proinflammatory versus tissue-protective responses remains poorly defined. We demonstrate that enteric neurons produce calcitonin gene-related peptide-related adrenomedullin 2 (ADM2) and identify a previously unrecognized role for the ADM2 pathway in promoting intestinal tissue-protective functions of group 2 innate lymphoid cells (ILC2s).
View Article and Find Full Text PDFNat Commun
July 2025
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Perception of external temperature is essential for maintaining homeostasis and avoiding thermal injury. Although molecular thermosensors such as transient receptor potential melastatin type 8 (TRPM8) have been identified, the neural circuits responsible for transmitting cool signals remain unclear. Here we show that a spinal circuit in mice conveys cool signals from the skin to the brain.
View Article and Find Full Text PDFEur J Pain
July 2025
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
Background: Breast cancer represents the most common cancer diagnosis and the leading cause of cancer-related death in women. Cancer is also associated with pain and changes in both tactile and temperature sensitivity that impair quality of life. While previous studies have investigated the effects of various chemotherapies in murine models of these symptoms, few have previously assessed the effects of cancer alone on these symptoms.
View Article and Find Full Text PDFJ Neuroinflammation
May 2025
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, China.
Background: Caveolin-1 (CAV1), a scaffolding protein critical for caveolae formation, regulates G-protein-coupled receptor (GPCR) signaling via caveolae-mediated endocytosis. The calcitonin receptor-like receptor (CLR), a GPCR and core subunit of the calcitonin gene-related peptide (CGRP) receptor, is a therapeutic target for migraine. However, the role of CAV1 in CLR regulation and migraine remains unclear.
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