Disrupting Hedgehog Cardin-Weintraub sequence and positioning changes cellular differentiation and compartmentalization in vivo

Development
Philipp KastlKay Grobe

Abstract

Metazoan Hedgehog (Hh) morphogens are essential regulators of growth and patterning at significant distances from their source, despite being produced as N-terminally palmitoylated and C-terminally cholesteroylated proteins, which firmly tethers them to the outer plasma membrane leaflet of producing cells and limits their spread. One mechanism to overcome this limitation is proteolytic processing of both lipidated terminal peptides, called shedding, but molecular target site requirements for effective Hh shedding remained undefined. In this work, by using Drosophila melanogaster as a model, we show that mutagenesis of the N-terminal Cardin-Weintraub (CW) motif inactivates recombinant Hh proteins to variable degrees and, if overexpressed in the same compartment, converts them into suppressors of endogenous Hh function. In vivo, additional removal of N-palmitate membrane anchors largely restored endogenous Hh function, supporting the hypothesis that proteolytic CW processing controls Hh solubilization. Importantly, we also observed that CW repositioning impairs anterior/posterior compartmental boundary maintenance in the third instar wing disc. This demonstrates that Hh shedding not only controls the differentiation of anterior c...Continue Reading

References

Jan 1, 1989·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·A D Cardin, H J Weintraub
Dec 2, 1994·Science·J J LeeP A Beachy
Oct 23, 1997·Nature·I Rodriguez, K Basler
Jun 5, 1998·The Journal of Biological Chemistry·R B PepinskyA Galdes
Feb 7, 2001·The Journal of Biological Chemistry·R B PepinskyE A Garber
Sep 2, 2003·Journal of Leukocyte Biology·Bruce WalcheckErik Matala
Sep 15, 2004·Trends in Genetics : TIG·Michèle CrozatierAlain Vincent
Nov 16, 2004·Molecular and Cellular Biology·Manuel Ascano, David J Robbins
Oct 4, 2005·BMC Developmental Biology·Rebecca J DawberMarcel van den Heuvel
Sep 3, 2008·Molecular Aspects of Medicine·Dylan R EdwardsCaroline J Pennington
Jan 30, 2009·The Journal of Biological Chemistry·Tabea DierkerKay Grobe
May 17, 2011·The Journal of Biological Chemistry·Pershang FarshiKay Grobe
Jun 15, 2011·Developmental Cell·Stefanie OhligKay Grobe
Nov 3, 2012·The Journal of Biological Chemistry·Stefanie OhligKay Grobe
Apr 9, 2013·The Journal of Biological Chemistry·Paul BaranChristoph Garbers
May 31, 2013·Nature Reviews. Molecular Cell Biology·James Briscoe, Pascal P Thérond
Oct 15, 2013·The Journal of Biological Chemistry·Katja Möller-HackbarthJürgen Scheller
Nov 28, 2013·The Journal of Biological Chemistry·Anders EtzerodtSøren Kragh Moestrup
Feb 14, 2014·Journal of Cell Science·Petra JakobsKay Grobe
Feb 22, 2014·Methods : a Companion to Methods in Enzymology·Tom A Hartl, Matthew P Scott
Jul 30, 2014·Developmental Biology·Thomas B Kornberg

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Citations

Apr 26, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dominique ManikowskiKay Grobe
Jun 27, 2019·International Journal of Molecular Sciences·Elizabeta MadzharovaUlrich Auf dem Keller
Jan 30, 2021·Frontiers in Cell and Developmental Biology·Dominique ManikowskiKay Grobe
Sep 14, 2021·Biochemical Society Transactions·Kristina Ehring, Kay Grobe

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