Palmitoylation of CD36/FAT regulates the rate of its post-transcriptional processing in the endoplasmic reticulum.
CD36/FAT is a transmembrane glycoprotein that functions in the cellular uptake of long-chain fatty acids and also as a scavenger receptor. As such it plays an important role in lipid homeostasis and, pathophysiologically, in the progression of type 2 diabetes and atherosclerosis. CD36 expression is tightly regulated at the levels of both transcription and translation. Here we show that its expression and location are also regulated post-translationally, by palmitoylation. Although palmitoylation of CD36 was not required for receptor maturation and cell surface expression, inhibition of palmitoylation either pharmacologically with cerulenin or by mutation of the relevant cysteines delayed processing at the ER and trafficking through the secretory pathway. The absence of palmitoylation also reduced the half life of the CD36 protein. Additionally, the CD36 palmitoylation mutant did not incorporate efficiently into lipid rafts, a site known to be required for its function of fatty acid uptake, and this reduced the efficiency of uptake of oxidized low density lipoprotein. These findings provide an added level of sophistication where translocation of CD36 to the plasma membrane may be physiologically regulated by palmitoylation.
Thorne
Rick F
RF
Cancer Research Unit, School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, NSW 2308, Australia. Rick.Thorne@newcastle.edu.au
Ralston
Kylie J
KJ
de Bock
Charles Edo
CE
Mhaidat
Nizar M
NM
Zhang
Xu Dong
XD
Boyd
Andrew W
AW
Burns
Gordon F
GF
D000215:Acylation; D000409:Alanine / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005434:Flow Cytometry; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008077:Lipoproteins, LDL / Q000378:metabolism; D054878:Lipoylation; D021962:Membrane Microdomains / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D012323:RNA Processing, Post-Transcriptional
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D003545:Cysteine; D000409:Alanine