Polarized sorting of Patched enables cytoneme‐mediated Hedgehog reception in the Drosophila wing disc
| Autor: | Isabel Guerrero, Carlos Jiménez-Jiménez, Milagros Guerra, Juan M. Falcón-Pérez, Laura González-Méndez, Esperanza Gonzalez, Ana-Citlali Gradilla, David Sánchez-Hernández, Gustavo Aguilar, Germán Andrés, Adrián Aguirre-Tamaral |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Patched
Vesicle fusion ESCRT Machinery endocrine system diseases Receptors Cell Surface Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Animals Drosophila Proteins Wings Animal Hedgehog Proteins Molecular Biology Hedgehog 030304 developmental biology 0303 health sciences Wing Endosomal Sorting Complexes Required for Transport General Immunology and Microbiology General Neuroscience Articles Extracellular vesicle Cell biology Protein Transport Drosophila melanogaster Imaginal Discs SNARE Proteins 030217 neurology & neurosurgery Adult stem cell Cytoneme |
| Zdroj: | EMBO J |
| ISSN: | 1460-2075 0261-4189 |
| Popis: | Hedgehog (Hh) signal molecules play a fundamental role in development, adult stem cell maintenance and cancer. Hh can signal at a distance, and we have proposed that its graded distribution across Drosophila epithelia is mediated by filopodia-like structures called cytonemes. Hh reception by Patched (Ptc) happens at discrete sites along presenting and receiving cytonemes, reminiscent of synaptic processes. Here, we show that a vesicle fusion mechanism mediated by SNARE proteins is required for Ptc placement at contact sites. Transport of Ptc to these sites requires multivesicular bodies (MVBs) formation via ESCRT machinery, in a manner different to that regulating Ptc/Hh lysosomal degradation after reception. These MVBs include extracellular vesicle (EV) markers and, accordingly, Ptc is detected in the purified exosomal fraction from cultured cells. Blockage of Ptc trafficking and fusion to basolateral membranes result in low levels of Ptc presentation for reception, causing an extended and flattened Hh gradient. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text