title: DHHC17 palmitoylates ClipR-59 and modulates ClipR-59 association with the plasma membrane.
abstract: ClipR-59 interacts with Akt and regulates Akt compartmentalization and Glut4 membrane trafficking in a plasma membrane association-dependent manner. The association of ClipR-59 with plasma membrane is mediated by ClipR-59 palmitoylation at Cys534 and Cys535. To understand the regulation of ClipR-59 palmitoylation, we have examined all known mammalian DHHC palmitoyltransferases with respect to their ability to promote ClipR-59 palmitoylation. We found that, among 23 mammalian DHHC palmitoyltransferases, DHHC17 is the major ClipR-59 palmitoyltransferase, as evidenced by the fact that DHHC17 interacted with ClipR-59 and palmitoylated ClipR-59 at Cys534 and Cys535. By palmitoylating ClipR-59, DHHC17 directly regulates ClipR-59 plasma membrane association, as ectopic expression of DHHC17 increased whereas silencing of DHHC17 reduced the levels of ClipR-59 associated with plasma membrane. We have also examined the role of DHHC17 in Akt signaling and found that silencing of DHHC17 in 3T3-L1 adipocytes decreased the levels of Akt as well as ClipR-59 on the plasma membrane and impaired insulin-dependent Glut4 membrane translocation. We suggest that DHHC17 is a ClipR-59 palmitoyltransferase that modulates ClipR-59 plasma membrane binding, thereby regulating Akt signaling and Glut4 membrane translocation in adipocytes.
authors.affiliation: Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: Wenying
authors.initials: W
authors.lastname: Ren
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Sun
authors.forename: Keyong
authors.initials: K
authors.lastname: Du
mesh_terms: D000217:Acyltransferases / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000502:physiology; D054878:Lipoylation; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C449670:CLIP3 protein, human; D051275:Glucose Transporter Type 4; D007328:Insulin; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C495692:SLC2A4 protein, human; D000217:Acyltransferases; C473038:ZDHHC17 protein, human; D051057:Proto-Oncogene Proteins c-akt