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Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates

Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex... Downloaded from genesdev.cshlp.org on December 12, 2021 - Published by Cold Spring Harbor Laboratory Press Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates 1 1 2 Miao-Hsueh Chen, Ya-Jun Li, Takatoshi Kawakami, Shan-Mei Xu, and Pao-Tien Chuang Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue in Hh signaling is to elucidate the molecular mechanism by which a Hh protein morphogen gradient is formed despite its membrane association. In this study, we used a combination of genetic, cellular, and biochemical approaches to address the role of lipid modifications in long-range vertebrate Hh signaling. Our molecular analysis of knockout mice deficient in Skn, the murine homolog of the Drosophila ski gene, which catalyzes Hh palmitoylation, and gene-targeted mice producing a nonpalmitoylated form of Shh indicates that Hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos. Furthermore, our biochemical data show that Hh lipid modifications are required for producing a soluble multimeric protein complex, which constitutes the major active component for Hh http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Genes & Development Unpaywall

Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates

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Unpaywall
ISSN
0890-9369
DOI
10.1101/gad.1185804
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Abstract

Downloaded from genesdev.cshlp.org on December 12, 2021 - Published by Cold Spring Harbor Laboratory Press Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates 1 1 2 Miao-Hsueh Chen, Ya-Jun Li, Takatoshi Kawakami, Shan-Mei Xu, and Pao-Tien Chuang Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue in Hh signaling is to elucidate the molecular mechanism by which a Hh protein morphogen gradient is formed despite its membrane association. In this study, we used a combination of genetic, cellular, and biochemical approaches to address the role of lipid modifications in long-range vertebrate Hh signaling. Our molecular analysis of knockout mice deficient in Skn, the murine homolog of the Drosophila ski gene, which catalyzes Hh palmitoylation, and gene-targeted mice producing a nonpalmitoylated form of Shh indicates that Hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos. Furthermore, our biochemical data show that Hh lipid modifications are required for producing a soluble multimeric protein complex, which constitutes the major active component for Hh

Journal

Genes & Development – Unpaywall

Published: Mar 15, 2004

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