Caveolin-2 palmitoylation turnover facilitates insulin receptor substrate-1-directed lipid metabolism by insulin receptor tyrosine kinase

Moonjeong Choi; Jaewoong Lee; Kyuho Jeong; Yunbae Pak

doi:10.1016/j.bbadis.2024.167173

Caveolin-2 palmitoylation turnover facilitates insulin receptor substrate-1-directed lipid metabolism by insulin receptor tyrosine kinase

Biochim Biophys Acta Mol Basis Dis. 2024 Apr 16;1870(5):167173. doi: 10.1016/j.bbadis.2024.167173. Online ahead of print.

Authors

Moonjeong Choi¹, Jaewoong Lee², Kyuho Jeong³, Yunbae Pak⁴

Affiliations

¹ Division of Life Science, Graduate School of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 52828, Republic of Korea.
² Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea.
³ Department of Biochemistry, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju 38066, Republic of Korea.
⁴ Division of Life Science, Graduate School of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 52828, Republic of Korea. Electronic address: ybpak@gnu.ac.kr.

PMID: 38631410
DOI: 10.1016/j.bbadis.2024.167173

Abstract

Here, we show that insulin induces palmitoylation turnover of Caveolin-2 (Cav-2) in adipocytes. Acyl protein thioesterases-1 (APT1) catalyzes Cav-2 depalmitoylation, and zinc finger DHHC domain-containing protein palmitoyltransferase 21 (ZDHHC21) repalmitoylation of the depalmitoylated Cav-2 for the turnover, thereby controlling insulin receptor (IR)-Cav-2-insulin receptor substrate-1 (IRS-1)-Akt-driven signaling. Insulin-induced palmitoylation turnover of Cav-2 facilitated glucose uptake and fat storage through induction of lipogenic genes. Cav-2-, APT1-, and ZDHHC21-deficient adipocytes, however, showed increased induction of lipolytic genes and glycerol release. In addition, white adipose tissues from insulin sensitive and resistant obese patients exhibited augmented expression of LYPLA1 (APT1) and ZDHHC20 (ZDHHC20). Our study identifies the specific enzymes regulating Cav-2 palmitoylation turnover, and reveals a new mechanism by which insulin-mediated lipid metabolism is controlled in adipocytes.

Keywords: APT1; Adipocyte lipid metabolism; Caveolin-2; Insulin receptor tyrosine kinase signaling; Palmitoylation turnover; ZDHHC21.