| First Author | Asciolla JJ | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 13 | Pages | 4608-4619.e4 |
| PubMed ID | 31875564 | Mgi Jnum | J:297026 |
| Mgi Id | MGI:6468877 | Doi | 10.1016/j.celrep.2019.11.110 |
| Citation | Asciolla JJ, et al. (2019) Hedgehog Acyltransferase Promotes Uptake of Palmitoyl-CoA across the Endoplasmic Reticulum Membrane. Cell Rep 29(13):4608-4619.e4 |
| abstractText | 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. |
