APT1 Depalmitoylates CD36 And Affects Its Plasma Membrane Localization

Palmitoylation is a reversible post-translational modification of proteins,in which 16-carbon palmitoic acid is covalently bound to cysteine residues on the side chains of proteins by means of thioester bonds,thereby regulating many physiological processes,such as protein stability,intracellular transport,and localization.Dynamic palmitoylation of proteins were catalyzed by Palmitoylase Acyltransferases composed of DHHC protein family and Depalmitoylases composed of acyl-protein thioesterases and ABHD proteins.APT1 is mainly located in mitochondria,a small part of which is also present in cytoplasm*.It is involved in the depalmitoylation of many signal proteins.MiRNA-138 inhibits the level of APT1 in the synaptic body of rats,and increases the membrane localization of G?13,thus changing the size of dendritic spines and synaptic transmission.CD36 is a transmembrane glycoprotein with 4 palmitoylation modification sites.As a class B scavenger receptor,CD36 mediates the uptake of oxidized low-density lipoprotein in cells,promoting the formation of atherosclerosis and triggering a series of inflammatory reactions.CD3 6 regulates fatty acid uptake in key tissues,which in turn affects lipid metabolism.At present,the studies of depalmitoylation mainly focus on neurobiology,but have not been reported in metabolic biology.In the previous paper published by our laboratory,we reported that DHHC5 can prevent the depalmitation of CD36 and maintain its localization on the plasma membrane.In this study,we identified APT1 as depalmitoylase of CD36 through immunofluorescence technology and Acyl-RAC assays.When APT1 and CD36 were co-transfected,CD3 6 could not localize on the plasma membrane.Treating with the inhibitor of depalmitoylase restored the plasma membrane localization of CD36.APT1 2nd cysteine and 119th serine both affect plasma membrane localization and palmitoylation of CD36.APT1 also affects the uptake of fatty acids by CD36.This study provides a theoretical basis for further revealing the dynamic palmitoylation of CD36 and the regulation of protein depalmitoylation on metabolism.Our current work is to explore the molecular mechanism of APT1 depalmitylates CD36 and the regulation mechanism of APT1 enzyme activity.