Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Nutrient deprivation ("starvation") is a major catabolic stress faced by mammalian cells in both pathological and physiological situations. Starvation induces autophagosome biogenesis in the immediate vicinity of ER and leads to lysosome spatial repositioning, but little is known about the consequences of nutritional stress on endosomes. Here, we report that starvation induces tethering of endosomal tubules to ER subregions, fostering autophagosome assembly. We show that this endosomal membrane generation is regulated by sorting nexin 1 (SNX1) protein and is important for the autophagic response. These newly formed SNX1 endosomal tubules establish connections with ER subdomains engaged in early autophagic machinery mobilization. Such endosome-ER transient tethers are regulated by a local dialog between SNX2, an endosomal partner of SNX1, and VAPB, an ER protein associated with autophagy initiation stage regulation. We propose that in a very early response to starvation, SNX1 and SNX2 cooperation induces and regulates endosomal membrane tubulation towards VAPB-positive ER subdomains involved in autophagosome biogenesis, highlighting the contribution of early endosomes in the cellular response to nutritional stress.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806675 | PMC |
| http://dx.doi.org/10.26508/lsa.202201652 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structure-Encoded Location Biased Signaling in a Class B GPCR: Focus on the PTH Type 1 Receptor.
Handb Exp Pharmacol
September 2025
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Research conducted over the last 15 years indicates that cAMP is generated not just from the plasma membrane but also from intracellular compartments, particularly in endosomes, where receptors are redistributed during the endocytosis process. This review centers on the parathyroid hormone type 1 receptor (PTHR) as a model for a peptide hormone GPCRs that generates cAMP from various locations with distinct duration and pharmacological effectiveness. We discuss how structural dynamics simulations aid in designing ligands that induce cAMP location bias, ultimately answering how the spatiotemporal generation of cAMP affects pharmacological responses mediated by the PTHR.
View Article and Find Full Text PDFMechanisms of Location Bias in G Protein-Coupled Receptors.
Handb Exp Pharmacol
September 2025
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
GPCRs are known for their versatile signaling roles at the plasma membrane; however, recent studies have revealed that these receptors also function within various intracellular compartments, such as endosomes, the Golgi apparatus, and the endoplasmic reticulum. This spatially distinct signaling, termed location bias, allows GPCRs to initiate unique signaling cascades and influence cellular processes-including cAMP production, calcium mobilization, and protein phosphorylation-in a compartment-specific manner. By mapping the impact of GPCR signaling from these subcellular locations, this chapter emphasizes the mechanisms underlying signaling from intracellular receptor pools in diversifying receptor functionality.
View Article and Find Full Text PDFA genetically encoded nanobody sensor reveals conformational diversity in β-arrestins orchestrated by distinct seven transmembrane receptors.
Proc Natl Acad Sci U S A
September 2025
Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India.
Agonist-induced interaction of G protein-coupled receptors (GPCRs) with β-arrestins (βarrs) is a critical mechanism that regulates the spatiotemporal pattern of receptor localization and signaling. While the underlying mechanism governing GPCR-βarr interaction is primarily conserved and involves receptor activation and phosphorylation, there are several examples of receptor-specific fine-tuning of βarr-mediated functional outcomes. Considering the key contribution of conformational plasticity of βarrs in driving receptor-specific functional responses, it is important to develop novel sensors capable of reporting distinct βarr conformations in cellular context.
View Article and Find Full Text PDFATG16L1 controls mammalian vacuolar proton ATPase.
J Cell Biol
October 2025
Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
The mechanisms governing mammalian proton pump V-ATPase function are of fundamental and medical interest. The assembly and disassembly of cytoplasmic V1 domain with the membrane-embedded V0 domain of V-ATPase is a key aspect of V-ATPase localization and function. Here, we show that the mammalian protein ATG16L1, primarily appreciated for its role in canonical autophagy and in noncanonical membrane atg8ylation processes, controls V-ATPase.
View Article and Find Full Text PDFAttenuation of IFITM proteins' antiviral activity through sequestration into intraluminal vesicles of late endosomes.
Front Immunol
September 2025
Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, United States.
Introduction: Interferon-induced transmembrane proteins (IFITMs) inhibit the entry of diverse enveloped viruses. The spectrum of antiviral activity of IFITMs is largely determined by their subcellular localization. IFITM1 localizes to and primarily blocks viral fusion at the plasma membrane, while IFITM3 prevents viral fusion in late endosomes by accumulating in these compartments.
View Article and Find Full Text PDF