AM and CGRP receptors undergo differential intracellular receptor trafficking upon ligand stimulation. Intracellular trafficking of CLR/RAMP receptor complexes is regulated by posttranslational modifications and protein-protein interactions that differ for each cell type. Recent evidence is accumulating to suggest that the RAMP isoform in complex with CLR may play a role in determining the intracellular trafficking and fate of ligand-stimulated receptor complexes. In this chapter, we will review the current literature on mechanisms of regulating receptor trafficking and roles that have been demonstrated for RAMPs in this regulation.
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http://dx.doi.org/10.1007/978-1-4614-2364-5_3 | DOI Listing |
Int J Mol Sci
January 2025
Centre of Biomedical Systems and Informatics, ZJU-UoE Institute, School of Medicine, International Campus, Zhejiang University, Haining 314400, China.
Colorectal cancer (CRC) is the third most common cancer globally, with limited effective biomarkers and sensitive therapeutic targets. An increasing number of studies have highlighted the critical role of tumor microenvironment (TME) imbalances, particularly immune escape due to impaired chemokine-mediated trafficking, in tumorigenesis and progression. Notably, CC chemokines (CCLs) have been shown to either promote or inhibit angiogenesis, metastasis, and immune responses in tumors, thereby influencing cancer development and patient outcomes.
View Article and Find Full Text PDFCells
January 2025
Department of Immunology and Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK.
Tissue fibrosis results from a dysregulated and chronic wound healing response accompanied by chronic inflammation and angiogenesis. Regardless of the affected organ, fibrosis shares the following common hallmarks: the recruitment of immune cells, fibroblast activation/proliferation, and excessive extracellular matrix deposition. Chemokines play a pivotal role in initiating and advancing these fibrotic processes.
View Article and Find Full Text PDFProtein Eng Des Sel
January 2025
Pfizer Rare Disease Research Unit, 610 Main Street, Cambridge, MA 02139, United States.
Pompe disease is a tissue glycogen disorder caused by genetic insufficiency of the GAA enzyme. GAA enzyme replacement therapies for Pompe disease have been limited by poor lysosomal trafficking of the recombinant GAA molecule through the native mannose-6-phosphate-mediated pathway. Here, we describe the successful rational engineering of a chimeric GAA enzyme that utilizes the binding affinity of a modified IGF-II moiety to its native receptor to bypass the mannose-6-phosphate-mediated lysosomal trafficking pathway, conferring a significant increase in cellular uptake of the GAA enzyme.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
IRCCS Humanitas Research Hospital, Rozzano, Italy
Background: ACKR2 is an atypical chemokine receptor that plays a significant role in regulating inflammation by binding to inflammatory CC chemokines and facilitating their degradation. Previous findings suggest that the genetic absence of ACKR2 leads to heightened tumor growth in inflammation-driven models. Conversely, mice lacking ACKR2 exhibit protection against lung metastasis in melanoma and breast cancer models.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Biochemistry, College of Life Science and Biotechnology, Brain Korea 21 Project, Yonsei University, Seoul 03722, Republic of Korea.
Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway.
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