Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing
Sabine Schürmann,
Georg Steffes,
Dominique Manikowski,
Philipp Kastl,
Ursula Malkus,
Shyam Bandari,
Stefanie Ohlig,
Corinna Ortmann,
Rocio Rebollido-Rios,
Mandy Otto,
Harald Nüsse,
Daniel Hoffmann,
Christian Klämbt,
Milos Galic,
Jürgen Klingauf,
Kay Grobe
Affiliations
Sabine Schürmann
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany
Georg Steffes
Center for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany; Institute of Neurobiology, University of Münster, Münster, Germany
Dominique Manikowski
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany
Philipp Kastl
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany
Ursula Malkus
Institute of Medical Physics and Biophysics, University of Münster, Münster, Germany
Shyam Bandari
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany
Stefanie Ohlig
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany
Corinna Ortmann
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany
Rocio Rebollido-Rios
Center for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany
Mandy Otto
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany
Harald Nüsse
Institute of Medical Physics and Biophysics, University of Münster, Münster, Germany
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany
Cell fate determination during development often requires morphogen transport from producing to distant responding cells. Hedgehog (Hh) morphogens present a challenge to this concept, as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producing cells. While several proposed Hh transport modes tie directly into these unusual properties, the crucial step of Hh relay from producing cells to receptors on remote responding cells remains unresolved. Using wing development in Drosophila melanogaster as a model, we show that Hh relay and direct patterning of the 3–4 intervein region strictly depend on proteolytic removal of lipidated N-terminal membrane anchors. Site-directed modification of the N-terminal Hh processing site selectively eliminated the entire 3–4 intervein region, and additional targeted removal of N-palmitate restored its formation. Hence, palmitoylated membrane anchors restrict morphogen spread until site-specific processing switches membrane-bound Hh into bioactive forms with specific patterning functions.
