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Polarized sorting of Patched enables cytoneme‐mediated Hedgehog reception in the Drosophila wing disc
Author(s) -
GonzálezMéndez Laura,
Gradilla AnaCitlali,
SánchezHernández David,
González Esperanza,
AguirreTamaral Adrián,
JiménezJiménez Carlos,
Guerra Milagros,
Aguilar Gustavo,
Andrés Germán,
FalcónPérez Juan M,
Guerrero Isabel
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019103629
Subject(s) - patched , hedgehog , biology , humanities , art , microbiology and biotechnology , signal transduction
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 ( MVB s) formation via ESCRT machinery, in a manner different to that regulating Ptc/Hh lysosomal degradation after reception. These MVB s 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.