The rapid activation of the mechanistic target of rapamycin complex-1 (mTORC1) by growth factors is increased by extracellular amino acids through yet-undefined mechanisms of amino acid transfer into endolysosomes. Because the endocytic process of macropinocytosis concentrates extracellular solutes into endolysosomes and is increased in cells stimulated by growth factors or tumor-promoting phorbol esters, we analyzed its role in amino acid–dependent activation of mTORC1. Here, we show that growth factor-dependent activation of mTORC1 by amino acids, but not glucose, requires macropinocytosis. In murine bone marrow–derived macrophages and murine embryonic fibroblasts stimulated with their cognate growth factors or with phorbol myristate acetate, activation of mTORC1 required an Akt-independent vesicular pathway of amino acid delivery into endolysosomes, mediated by the actin cytoskeleton. Macropinocytosis delivered small, fluorescent fluid-phase solutes into endolysosomes sufficiently fast to explain growth factor–mediated signaling by amino acids. Therefore, the amino acid–laden macropinosome is an essential and discrete unit of growth factor receptor signaling to mTORC1
The information and education environment refers to: 1) the presence of information infrastructures such as broadband Internet access and public libraries in a location; 2) a person’s proximity to information infrastructures and sources; 3) the distribution of information infrastructures, sources and in a specific location; and 4) exposure to specific messages (information content) within a specific location.
Coverage for all data: 10-county Detroit-Warren-Ann Arbor Combined Statistical Area.
The dataset represents the complete, reproducible search strategies for all literature databases searched during the systematic review. The Endnote file and the Endnote import files contain all citations considered for inclusion in the review.
The dataset includes the reproducible search strategies for all literature databases searched during the review, the key articles used to generate relevant search terms and test the effectiveness of the searches, the Endnote library that has all citations considered for inclusion, a flow chart describing the screening process, and the screening forms used for inclusion and exclusion.
Data include variables used to run mixed effects models examining the association between the nose/throat microbiome and influenza virus infection. Certain individual participant data have been excluded due to identifiability concerns. Data also include the oligotype count table and taxonomic classifications. and Curation Notes: Readme updated Nov. 29, 2018 with context for oligotype and taxonomy files, and citation to associated article.
Data include variables used to run accelerated failure time models examining the association between the nose/throat microbiome and 1) symptom duration, 2) shedding duration, and 3) time to infection. Certain individual participant data have been excluded due to identifiability concerns. Data also include the oligotype count table and taxonomic classifications.
The research adheres to PRISMA-HARM recommendations for systematic reviews. The reproducible search strategies for all databases, the citation export files from all databases, and the eligibility screening decisions are included in the dataset.