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Biophys J. 2014 Jan 7;106(1):93-105. doi: 10.1016/j.bpj.2013.11.024.

The autodepalmitoylating activity of APT maintains the spatial organization of palmitoylated membrane proteins.

Author information

1
Department of Systemic Cell Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany.
2
Department of Chemical Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany; Faculty of Chemistry, Technical University Dortmund, Dortmund, Germany.
3
Department of Chemical Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany.
4
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.

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.

PMID:
24411241
PMCID:
PMC3907232
DOI:
10.1016/j.bpj.2013.11.024
[Indexed for MEDLINE]
Free PMC Article

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