Lgr4 and Lgr5 drive the formation of long actin-rich cytoneme-like membrane protrusions
| Autor: | H. Kim Lyerly, Lauren K. Rochelle, Larry S. Barak, Marc G. Caron, Sébastien Marion, Joshua C. Snyder |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Cell signaling Arrestins Blotting Western Cell Surface Extension Biology Receptors G-Protein-Coupled Cell membrane Cancer stem cell Myosin medicine Humans Immunoprecipitation Pseudopodia Molecular Biology Actin Tissue homeostasis beta-Arrestins Beta-Arrestins Stem Cells Cell Membrane LGR5 Biological Transport Cell Biology beta-Arrestin 2 Actins Cell biology medicine.anatomical_structure HEK293 Cells Cell Surface Extensions Filopodia Developmental Biology Cytoneme Signal Transduction Research Article |
| Zdroj: | Journal of cell science. 128(6) |
| ISSN: | 1477-9137 |
| Popis: | Embryonic development and adult tissue homeostasis require precise information exchange between cells and their microenvironment to coordinate cell behavior. A specialized class of ultra-long actin-rich filopodia, termed cytonemes, provides one mechanism for this spatiotemporal regulation of extracellular cues. We provide here a mechanism whereby the stem-cell marker Lgr5, and its family member Lgr4, promote the formation of cytonemes. Lgr4- and Lgr5-induced cytonemes exceed lengths of 80 µm, are generated through stabilization of nascent filopodia from an underlying lamellipodial-like network and functionally provide a pipeline for the transit of signaling effectors. As proof-of-principle, we demonstrate that Lgr5-induced cytonemes act as conduits for cell signaling by demonstrating that the actin motor and filopodial cargo carrier protein myosin X (Myo10) and the G-protein-coupled receptor (GPCR) signaling effector β-arrestin-2 (Arrb2) transit into cytonemes. This work delineates a biological function for Lgr4 and Lgr5 and provides the rationale to fully investigate Lgr4 and Lgr5 function and cytonemes in mammalian stem cell and cancer stem cell behavior. |
| Databáze: | OpenAIRE |
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