Hedgehog acyltransferase promotes uptake of palmitoyl-CoA across the endoplasmic reticulum membrane Journal Article
| Authors: | Asciolla, J. J.; Resh, M. D. |
| Article Title: | Hedgehog acyltransferase promotes uptake of palmitoyl-CoA across the endoplasmic reticulum membrane |
| Abstract: | Attachment of palmitate to the N terminus of Sonic hedgehog (Shh) is essential for Shh signaling. Shh palmitoylation is catalyzed on the luminal side of the endoplasmic reticulum (ER) by Hedgehog acyltransferase (Hhat), an ER-resident enzyme. Palmitoyl-coenzyme A (CoA), the palmitate donor, is produced in the cytosol and is not permeable across membrane bilayers. It is not known how palmitoyl-CoA crosses the ER membrane to access the active site of Hhat. Here, we use fluorescent and radiolabeled palmitoyl-CoA probes to demonstrate that Hhat promotes the uptake of palmitoyl-CoA across the ER membrane in microsomes and semi-intact cells. Reconstitution of purified Hhat into liposomes provided further evidence that palmitoyl-CoA uptake activity is an intrinsic property of Hhat. Palmitoyl-CoA uptake was regulated by and could be uncoupled from Hhat enzymatic activity, implying that Hhat serves a dual function as a palmitoyl acyltransferase and a conduit to supply palmitoyl-CoA to the luminal side of the ER. © 2019 The Author(s) Palmitoylation of hedgehog proteins by Hedgehog acyltransferase (Hhat) occurs on the luminal side of the ER. However, the palmitoyl-CoA donor for the reaction is membrane impermeable. Asciolla and Resh show that Hhat serves a dual function as both an acyltransferase and a transporter that promotes palmitoyl-CoA uptake across the ER membrane. © 2019 The Author(s) |
| Keywords: | controlled study; protein expression; unclassified drug; enzyme activity; endoplasmic reticulum; catalysis; sonic hedgehog; enzyme purification; bioaccumulation; liposome; acyltransferase; hydrophilicity; hedgehog acyltransferase; palmitoyl coenzyme a; protein palmitoylation; microsome; priority journal; article; endoplasmic reticulum membrane; palmitoyl-coa |
| Journal Title: | Cell Reports |
| Volume: | 29 |
| Issue: | 13 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2019-12-24 |
| Start Page: | 4608 |
| End Page: | 4619.e4 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2019.11.110 |
| PROVIDER: | scopus |
| PUBMED: | 31875564 |
| PMCID: | PMC6948154 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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