GOLGA7B

GOLGA7B is an S-acylated accessory subunit of plasma membrane palmitoyltransferase complexes that controls the stability, localization, and substrate output of DHHC5/ZDHHC5 (PMID:31402609). DHHC5 binds and palmitoylates GOLGA7B, and this palmitoylation prevents clathrin-mediated endocytosis of DHHC5, retaining the enzyme at the plasma membrane (PMID:31402609). GOLGA7B selectively stabilizes DHHC5 and DHHC8 — but not other DHHC9-subfamily members — through their conserved C-terminal cysteine motif, defining the specificity of the accessory interaction (PMID:37035671). The resulting DHHC5/GOLGA7B complex palmitoylates desmosomal substrates desmoglein-2 and plakophilin-3, directing desmoglein-2 to the plasma membrane and supporting desmosomal patterning and cell adhesion (PMID:31402609). Complex assembly is dynamically regulated: AMPK phosphorylation of ZDHHC5 at Ser296/Ser380 weakens the ZDHHC5–GOLGA7B interaction and displaces the enzyme from the plasma membrane, reducing NOD1 palmitoylation and attenuating innate immune signaling (PMID:41890956).

1. 2019 High

   Established that GOLGA7B is both a substrate and a functional partner of DHHC5, explaining how the palmitoyltransferase is retained at the plasma membrane rather than internalized.

   Evidence Co-immunoprecipitation, palmitoylation assays, clathrin-mediated endocytosis inhibition, and membrane localization imaging

   PMID:31402609

   Open questions at the time

   • Structural basis of the DHHC5–GOLGA7B interaction not resolved
   • Whether GOLGA7B palmitoylation sites are necessary and sufficient for endocytosis blockade not fully mapped
2. 2019 High

   Connected the DHHC5/GOLGA7B complex to a concrete biological output by identifying desmosomal substrates and an adhesion phenotype, moving the complex beyond a self-stabilization loop.

   Evidence Proteomics of complex-associated proteins, knockdown loss-of-function, substrate palmitoylation, localization and cell adhesion assays

   PMID:31402609

   Open questions at the time

   • Direct versus indirect palmitoylation of plakophilin-3 not dissected
   • In vivo physiological relevance to tissue adhesion not tested
3. 2023 Medium

   Defined the selectivity of GOLGA7B accessory function, showing it stabilizes DHHC5 and DHHC8 specifically via their conserved C-terminal cysteine motif rather than acting as a general DHHC chaperone.

   Evidence Co-expression stability assays, size-exclusion chromatography, and in vitro palmitoyl acyltransferase activity assays

   PMID:37035671

   Open questions at the time

   • Single lab with no independent replication
   • Precise residues mediating the CCM-dependent interaction not pinpointed
   • Quantitative effect on enzyme catalytic rate versus stability not separated
4. 2026 Medium

   Identified a signaling input that dynamically regulates complex assembly, showing AMPK phosphorylation of ZDHHC5 disassembles the GOLGA7B interaction to tune innate immune palmitoylation.

   Evidence Biochemical phosphorylation assays, reciprocal Co-IP, membrane localization imaging, and NOD1 signaling readouts in immune-competent cells

   PMID:41890956

   Open questions at the time

   • Single lab with no independent replication
   • Whether GOLGA7B itself is modified during this regulation untested
   • Upstream stimuli activating AMPK in this context not defined

• How GOLGA7B integrates its desmosomal-adhesion and innate-immune roles, and whether its own acylation state is itself a regulatory node, remains unresolved.
• No structural model of the GOLGA7B–DHHC complex
• No in vivo or organismal phenotype reported
• Regulation of GOLGA7B abundance/turnover uncharacterized