title: The autodepalmitoylating activity of APT maintains the spatial organization of palmitoylated membrane proteins.
abstract: The localization and signaling of S-palmitoylated peripheral membrane proteins is sustained by an acylation cycle in which acyl protein thioesterases (APTs) depalmitoylate mislocalized palmitoylated proteins on endomembranes. However, the APTs are themselves reversibly S-palmitoylated, which localizes thioesterase activity to the site of the antagonistc palmitoylation activity on the Golgi. Here, we resolve this conundrum by showing that palmitoylation of APTs is labile due to autodepalmitoylation, creating two interconverting thioesterase pools: palmitoylated APT on the Golgi and depalmitoylated APT in the cytoplasm, with distinct functionality. By imaging APT-substrate catalytic intermediates, we show that it is the depalmitoylated soluble APT pool that depalmitoylates substrates on all membranes in the cell, thereby establishing its function as release factor of mislocalized palmitoylated proteins in the acylation cycle. The autodepalmitoylating activity on the Golgi constitutes a homeostatic regulation mechanism of APT levels at the Golgi that ensures robust partitioning of APT substrates between the plasma membrane and the Golgi.
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany.
authors.forename: Nachiket
authors.initials: N
authors.lastname: Vartak
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Papke
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany.
authors.forename: Hernan E
authors.initials: HE
authors.lastname: Grecco
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany.
authors.forename: Lisaweta
authors.initials: L
authors.lastname: Rossmannek
authors.affiliation: Department of Chemical Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany; Faculty of Chemistry, Technical University Dortmund, Dortmund, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.affiliation: Department of Chemical Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hedberg
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany; Faculty of Chemistry, Technical University Dortmund, Dortmund, Germany. Electronic address: philippe.bastiaens@mpi-dortmund.mpg.de.
authors.forename: Philippe I H
authors.initials: PI
authors.lastname: Bastiaens
mesh_terms: D000215:Acylation; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004285:Dogs; D006056:Golgi Apparatus / Q000378:metabolism; D054878:Lipoylation; D061985:Madin Darby Canine Kidney Cells; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D013869:Thiolester Hydrolases / Q000378:metabolism*
chemical_list: D013869:Thiolester Hydrolases