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DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane.
- Source :
-
Cell reports [Cell Rep] 2019 Jan 02; Vol. 26 (1), pp. 209-221.e5. - Publication Year :
- 2019
-
Abstract
- Fatty acid uptake is the first step in fatty acid utilization, but it remains unclear how the process is regulated. Protein palmitoylation is a fatty acyl modification that plays a key regulatory role in protein targeting and trafficking; however, its function in regulating fatty acid metabolism is unknown. Here, we show that two of the Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC4 and DHHC5, regulate fatty acid uptake. DHHC4 and DHHC5 function at different subcellular localizations to control the palmitoylation, plasma membrane localization, and fatty acid uptake activity of the scavenger receptor CD36. Depletion of either DHHC4 or DHHC5 in cells disrupts CD36-dependent fatty acid uptake. Furthermore, both Dhhc4 <superscript>-/-</superscript> and adipose-specific Dhhc5 knockout mice show decreased fatty acid uptake activity in adipose tissues and develop severe hypothermia upon acute cold exposure. These findings demonstrate a critical role of DHHC4 and DHHC5 in regulating fatty acid uptake.<br /> (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- 3T3-L1 Cells
Adipose Tissue metabolism
Amino Acid Sequence
Animals
Biological Transport
Cell Membrane metabolism
HEK293 Cells
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Transfection
Acyltransferases metabolism
CD36 Antigens metabolism
Fatty Acids metabolism
Lipoylation
Membrane Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 26
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 30605677
- Full Text :
- https://doi.org/10.1016/j.celrep.2018.12.022