Affinage

GORASP2

Golgi reassembly-stacking protein 2 · UniProt Q9H8Y8

Length
452 aa
Mass
47.1 kDa
Annotated
2026-06-10
46 papers in source corpus 30 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GORASP2/GRASP55 is a peripheral medial-Golgi membrane protein that tethers adjacent cisternae into stacks and the Golgi ribbon, organizing the Golgi as a platform for accurate secretory transport and glycosylation (PMID:10487747, PMID:28814501). Stacking is achieved through homotypic trans-oligomerization of its N-terminal tandem-PDZ GRASP domain, whose crystal structure reveals reciprocal PDZ2-PDZ2 dimerization combined with C-terminal tail insertion into the PDZ1 pocket of an adjacent dimer, both contacts being required for membrane tethering (PMID:20083603, PMID:23940043). This activity is gated by post-translational modification: mitotic phosphorylation by MEK/ERK and CDK1 at T225/T249 within the C-terminal serine/proline-rich region, PKCα phosphorylation downstream of Ca2+, K50 acetylation reversed by SIRT2, and mTORC1-dependent phosphorylation collectively control Golgi unlinking, post-mitotic reassembly, and stress-induced relocalization (PMID:18434598, PMID:20083603, PMID:31604796, PMID:32179476, PMID:34245671, PMID:40288664). As a PDZ scaffold GRASP55 binds the golgin-45–Rab2 effector complex on the medial-Golgi and engages C-terminal valine/PDZ-motif-bearing cargo—TGF-alpha, CD8alpha, Frizzled4, CD83, JAM-B/C, and Cx36—to govern their Golgi retention, glycosylation, and surface delivery (PMID:11101516, PMID:11739401, PMID:19840934, PMID:25701785, PMID:28617811, PMID:39395036). At the trans-Golgi it retains glycosphingolipid biosynthesis enzymes by blocking their COPI-mediated retrograde escape and maintains GOLPH3-dependent stability of LYSET/GNPTAB for mannose-6-phosphate tagging, so that its loss missorts lysosomal enzymes such as HEXA and disrupts lysosomal mTORC1 signaling (PMID:34516001, PMID:39841559, PMID:41991615). Upon nutrient stress, demodified GRASP55 (loss of O-GlcNAcylation or mTORC1/mTORC1-dependent phosphorylation) redistributes from the Golgi to autophagic membranes, where it tethers LC3-II-bearing autophagosomes to LAMP2-bearing lysosomes, promotes phagophore closure via VPS4A–ESCRT-III and autophagosome-lysosome fusion via RAB7A–HOPS–SNARE machinery, and drives unconventional secretion of cargo including IL-1β, MMP2, and mutant huntingtin (PMID:29689198, PMID:30894053, PMID:34245671, PMID:35780830, PMID:39056394, PMID:30880003). Gorasp2 knockout mice reveal physiological roles in spermatogenesis/acrosome formation, intestinal lipid absorption and chylomicron secretion, and dendritic-cell MHC sorting for antigen presentation (PMID:28617811, PMID:32184397, PMID:39955774).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1999 High

    Established the foundational function of GRASP55 as a Golgi cisternal stacking factor, answering whether a defined protein mediates Golgi architecture.

    Evidence Cryo-EM localization to medial-Golgi plus a cell-free stacking assay blocked by recombinant protein and antibodies

    PMID:10487747

    Open questions at the time
    • Did not resolve the molecular contacts mediating stacking
    • Distinct from GM130-binding GRASP65 but partner network unknown
  2. 2000 High

    Defined GRASP55 as a membrane-anchored PDZ scaffold for transmembrane cargo, showing its first PDZ domain binds the TGF-alpha C-terminus to control surface delivery.

    Evidence Protein purification, PDZ binding and TGF-alpha C-terminal mutagenesis with surface-expression readout

    PMID:11101516

    Open questions at the time
    • Generality of C-terminal PDZ-cargo recognition not yet established
    • Lipidation contribution to function untested
  3. 2001 High

    Placed GRASP55 in a defined effector complex by showing it binds golgin-45 and GTP-Rab2 to support Golgi structure and secretory transport.

    Evidence Reciprocal Co-IP, yeast two-hybrid, and golgin-45 depletion with secretory transport assay

    PMID:11739401

    Open questions at the time
    • Structural basis of the GRASP55-golgin-45 interaction unresolved at this stage
    • How Rab2 GTP-loading is coupled to the complex unknown
  4. 2008 High

    Showed GRASP55 stacking is regulated by mitotic phosphorylation, linking Golgi unlinking to cell-cycle entry.

    Evidence MEK/ERK phosphosite mapping (T225/T249), phosphomimetic gene replacement and in vitro fragmentation/mitotic-entry peptide assays

    PMID:18385516 PMID:18434598

    Open questions at the time
    • Identity of the component released by phosphorylation not defined
    • Phosphatase reversing the modification unknown
  5. 2009 High

    Generalized PDZ-cargo recognition by demonstrating GRASP55 binds C-terminal valine receptors CD8alpha and Frizzled4 and acts sequentially with GRASP65 in their transport.

    Evidence Direct PDZ pull-down and siRNA knockdown with cargo-specific trafficking assays

    PMID:19840934

    Open questions at the time
    • Sequential GRASP55/GRASP65 hand-off mechanism not detailed
  6. 2010 High

    Mapped stacking to N-terminal GRASP-domain oligomerization regulated by C-terminal phosphorylation, mechanistically separating stacking from regulation.

    Evidence siRNA knockdown, phospho/nonphospho mutant expression, Golgi morphology quantification and in vitro oligomerization assay

    PMID:20083603

    Open questions at the time
    • Atomic detail of oligomer interface still lacking at this stage
  7. 2013 High

    Provided the structural mechanism of stacking and uncovered that GRASPs restrain trafficking to ensure glycosylation fidelity.

    Evidence X-ray crystallography of the GRASP domain with mutagenesis, plus knockdown trafficking/glycomics/sorting analyses

    PMID:23552074 PMID:23940043

    Open questions at the time
    • How stacking slows transport to permit glycosylation not mechanistically resolved
    • In vivo relevance not yet tested with knockout
  8. 2015 Medium

    Extended the PDZ-cargo repertoire to CD83 in dendritic cells via a C-terminal TELV motif controlling glycosylation and surface expression.

    Evidence Yeast two-hybrid, Co-IP, TELV-motif mutagenesis with glycosylation and surface readouts

    PMID:25701785

    Open questions at the time
    • Single lab; physiological consequence for DC function not addressed here
  9. 2017 High

    Delivered high-resolution structures and in vivo validation, defining a two-site golgin-45 binding mode and demonstrating GRASP55 requirement in mouse spermatogenesis through JAM interactions.

    Evidence Crystal structures of GRASP55-golgin-45 and GRASP55-JAM complexes, Gorasp2 knockout mouse phenotyping and small-molecule (Graspin) inhibition

    PMID:28049725 PMID:28617811

    Open questions at the time
    • Functional role of the observed zinc-finger structure unclear
    • Tissue specificity of JAM-dependent functions not fully mapped
  10. 2017 High

    Confirmed with rigorous genetics that GRASP55/65 maintain stacked Golgi structure required for accurate protein and lipid glycosylation.

    Evidence CRISPR single/double knockout with EM, trafficking and glycan analyses

    PMID:28814501

    Open questions at the time
    • Redundancy between GRASP55 and GRASP65 not fully partitioned
  11. 2018 High

    Discovered a stress-regulated relocalization mechanism: de-O-GlcNAcylated GRASP55 leaves the Golgi to tether autophagosomes to lysosomes.

    Evidence O-GlcNAcylation assays, live imaging, Co-IP with LC3-II/LAMP2, and autophagic flux with modification-deficient mutant

    PMID:29689198

    Open questions at the time
    • OGT site(s) on GRASP55 and the de-modifying enzyme not defined
    • Whether tethering is direct membrane bridging unresolved
  12. 2019 High

    Expanded the autophagy role to PtdIns3K-UVRAG assembly and connected GRASP55 to unconventional IL-1β secretion via the IRE1α UPR branch.

    Evidence Co-IP with BECN1/LC3/LAMP2 and depletion flux assays; knockout macrophage IL-1β secretion with IRE1α pathway epistasis

    PMID:30880003 PMID:30894053

    Open questions at the time
    • How GRASP55 couples to IRE1α mechanistically unknown
    • Direct vs scaffolding role in UVRAG complex not separated
  13. 2019 High

    Identified acetylation control of Golgi reassembly, with SIRT2 deacetylating GRASP55 K50 to restore post-mitotic Golgi structure.

    Evidence Co-IP, SIRT2 knockdown, and double-KO complementation with K50R/K50Q mutants and morphology readouts

    PMID:31604796

    Open questions at the time
    • Acetyltransferase adding K50 not identified
    • How K50 acetylation alters self-interaction structurally unclear
  14. 2020 High

    Resolved temporal/redundancy questions and added kinase and physiological inputs: rapid degron showed neither GRASP alone is needed for stacking, PKCα directly phosphorylates GRASP55 downstream of Ca2+, and GRASP55 supports intestinal lipid absorption.

    Evidence Auxin-degron imaging/EM, in vitro PKCα kinase assay with pharmacology, and Gorasp2 knockout mouse lipid/chylomicron phenotyping

    PMID:32179476 PMID:32184397 PMID:33301566

    Open questions at the time
    • Reconciling acute degron vs chronic-loss stacking phenotypes incomplete
    • PKCα phosphosites on GRASP55 not mapped
  15. 2021 High

    Established mTORC1 as the master regulator coupling nutrient/stress sensing to GRASP55 relocalization and unconventional secretion, and defined a trans-Golgi role in retaining glycosphingolipid enzymes against COPI retrograde escape.

    Evidence In vitro mTORC1 kinase assay with secretome proteomics; KO cells with Co-IP, COPI budding assay and lipidomics

    PMID:34245671 PMID:34516001

    Open questions at the time
    • mTORC1 phosphosite-to-relocalization causality not fully dissected
    • Selectivity for GSL enzymes vs other COPI cargo unknown
  16. 2021 Medium

    Indicated GRASP55 restricts early autophagosome formation and mapped a proximal ER-Golgi interactome.

    Evidence KO LC3-puncta quantification, BioID proximity proteomics, and ER-Golgi marker imaging

    PMID:34533192

    Open questions at the time
    • Mechanistic basis of restricting autophagosome biogenesis inferential
    • Single lab; BioID hits not functionally validated
  17. 2022 High

    Defined a dual mechanism for unconventional secretion of mutant huntingtin: autophagosome-lysosome tethering and stabilization of the TMED10/p23 translocation channel.

    Evidence KO secretion/secretomics, Co-IP with p23/TMED10 and autophagosome-lysosome fusion assays

    PMID:35780830

    Open questions at the time
    • How GRASP55 stabilizes TMED10 structurally unknown
    • Relative contribution of the two routes per cargo unclear
  18. 2024 High

    Resolved molecular steps of autophagic membrane closure and fusion, linking GORASP2 to VPS4A-ESCRT-III phagophore closure and RAB7A-GEF/HOPS/SNARE-driven fusion.

    Evidence Super-resolution imaging, depletion with proteinase-K closure assay, ESCRT/VPS4A and RAB7A-GEF assays, and SNARE complex Co-IP

    PMID:39056394

    Open questions at the time
    • Direct vs indirect regulation of VPS4A and MON1A-CCZ1 not fully separated
  19. 2024 Medium

    Extended PDZ-motif cargo control to the gap-junction protein Cx36, stabilizing it in the Golgi against COPII-mediated ER export.

    Evidence siRNA, BioID, Co-IP and Cx36 trafficking assays in HEK293T with SAYV-motif analysis

    PMID:39395036

    Open questions at the time
    • Single lab/overexpression context
    • How GRASP55 antagonizes COPII export mechanistically unclear
  20. 2025 High

    Established GRASP55 control of lysosomal enzyme biogenesis via the GOLPH3-LYSET-GNPTAB axis for M6P tagging, with consequences for HEXA sorting and lysosomal mTORC1 signaling.

    Evidence KO secretomics, HEXA processing/M6P-receptor Co-IP, GOLPH3 binding and LYSET/GNPTAB stability assays, and selective TFEB/TFE3 phosphorylation readouts

    PMID:39841559 PMID:41991615

    Open questions at the time
    • Whether GRASP55-GOLPH3 binding is direct or complex-mediated not fully resolved
    • Breadth of affected lysosomal hydrolases beyond HEXA incomplete
  21. 2025 High

    Showed GRASP55 specifically supports immune antigen presentation by sorting MHC-I/II in dendritic cell phagosomes.

    Evidence CRISPR KO BMDCs, multiple antigen-type presentation assays, phagosome recruitment imaging and MHC trafficking

    PMID:39955774

    Open questions at the time
    • Molecular partner recognizing MHC for sorting not identified
  22. 2025 Medium

    Connected GRASP55 phosphorylation to disease-relevant Golgi stress, with CDK1 phosphorylating T225 to exacerbate neuronal injury after intracerebral hemorrhage.

    Evidence In vitro CDK1 kinase assay, T225 mutagenesis and CDK1 knockdown in an ICH rat model with apoptosis/Golgi-stress readouts

    PMID:40288664

    Open questions at the time
    • Single lab; mechanistic link from T225 phosphorylation to neuronal apoptosis indirect
    • Generalizability beyond ICH model untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the integrated set of post-translational modifications is decoded to switch GRASP55 between Golgi stacking, cargo retention, and autophagic/secretory tethering—and the structural basis of its membrane-bridging on autophagic membranes—remains unresolved.
  • No integrated model of how competing modifications set localization
  • Direct membrane-tethering topology on autophagosome/lysosome not structurally defined
  • Enzymes adding several modifications (acetyltransferase, full mTORC1/PKCα site set) incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0140313 molecular sequestering activity 4
Localization
GO:0005794 Golgi apparatus 6 GO:0005764 lysosome 4 GO:0031410 cytoplasmic vesicle 3 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-9609507 Protein localization 7 R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-9612973 Autophagy 5 R-HSA-1640170 Cell Cycle 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-168256 Immune System 2
Partners
CD83GOLGA2GOLPH3JAM-CLAMP2MAP1LC3BRAB2ATGFA
Complex memberships
GRASP55-golgin-45-Rab2 effector complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 GRASP55 is a peripheral Golgi membrane protein localized to the medial-Golgi cisternae (as determined by cryo-electron microscopy) that functions in the stacking of Golgi cisternae; recombinant GRASP55 and antibodies to the protein block Golgi cisternal stacking in a cell-free system. Cryo-electron microscopy for localization; cell-free Golgi stacking assay with recombinant protein and blocking antibodies The EMBO journal High 10487747
1999 GRASP55 does not detectably bind GM130 by biochemical methods, though a weak interaction was detected in the yeast two-hybrid system, distinguishing it from GRASP65 which binds GM130 directly. Biochemical pulldown (negative result) and yeast two-hybrid The EMBO journal Medium 10487747
2000 GRASP55 (p59) is myristoylated and palmitoylated, associates with the Golgi system, and its first PDZ domain interacts directly with the C-terminus of transmembrane TGF-alpha; C-terminal mutations of TGF-alpha that abolish interaction with GRASP55 strongly impair TGF-alpha cell surface expression. Protein purification, cDNA cloning, co-localization, PDZ domain binding assay, mutagenesis of TGF-alpha C-terminus with surface expression readout The EMBO journal High 11101516
2001 GRASP55 forms a complex with the coiled-coil protein golgin-45 and the GTP-bound form of rab2; depletion of golgin-45 disrupts the Golgi apparatus and blocks secretory protein transport, establishing a GRASP55–golgin-45–rab2 effector complex on the medial-Golgi essential for Golgi structure and protein transport. Co-immunoprecipitation, yeast two-hybrid, functional depletion with secretory transport assay The Journal of cell biology High 11739401
2008 GRASP55 is a target of MEK/ERK phosphorylation at mitosis; depletion of GRASP55 fragments the Golgi ribbon and suppresses the MEK1 requirement for the G2/M cell cycle transition; aspartic acid substitutions mimicking mitotic phosphorylation of GRASP55 are sufficient to unlink the Golgi apparatus in a gene replacement assay. siRNA knockdown with Golgi morphology readout, gene replacement with phosphomimetic mutants, cell cycle progression assay Molecular biology of the cell High 18434598
2008 GRASP55 is mitotically phosphorylated at threonine 225 and threonine 249; wild-type peptides containing these residues inhibit Golgi fragmentation and cell entry into mitosis in vitro, while phosphomimetic T225E/T249E mutant peptides do not, suggesting phosphorylation at these sites releases a bound component required for Golgi fragmentation. Phospho-peptide mapping, in vitro Golgi fragmentation assay, cell mitosis entry assay with wild-type and phosphomimetic peptides Molecular biology of the cell High 18385516
2009 GRASP55 PDZ domains bind directly to the C-terminal valine-bearing receptors CD8alpha and Frizzled4, and both GRASP55 and GRASP65 are required sequentially for efficient transport of these receptors to and through the Golgi complex. Direct PDZ domain binding assay (pull-down), siRNA knockdown with trafficking assay for C-terminal valine-bearing cargo The Journal of biological chemistry High 19840934
2010 GRASP55 stacks Golgi membranes by forming oligomers through its N-terminal GRASP domain; this process is regulated by phosphorylation within the C-terminal serine/proline-rich domain; siRNA depletion of GRASP55 reduces cisternae per stack, and expression of nonphosphorylatable GRASP55 mutants enhances Golgi stacking in interphase and inhibits Golgi disassembly during mitosis. siRNA knockdown, expression of phosphomimetic and nonphosphorylatable mutants, Golgi morphology quantification, in vitro oligomerization assay The Journal of cell biology High 20083603
2013 Crystal structures of the GRASP domain of GRASP55 reveal homotypic interactions: the GRASP domain forms a dimer in which PDZ2 peptide-binding pockets face each other, and dimers are further connected by the C-terminal tail of one GRASP domain inserting into the PDZ1 pocket of another dimer; biochemical analysis confirms both contact types are needed for GRASP-mediated Golgi stacking. X-ray crystallography, biochemical binding assays, mutagenesis The Journal of biological chemistry High 23940043
2013 CRISPR/RNAi knockdown of GRASP55 accelerates protein trafficking through Golgi membranes and has striking negative effects on protein glycosylation and sorting; these effects are not caused by Golgi ribbon unlinking, unconventional secretion, or ER stress, identifying GRASP55/65 as negative regulators of exocytic transport needed for proper glycosylation. siRNA knockdown, protein trafficking assay, glycan analysis (mass spectrometry), sorting assay Nature communications High 23552074
2015 GRASP55 interacts with CD83 via its C-terminal TELV-motif in human dendritic cells; mutation of the TELV-motif disrupts GRASP55 binding and alters CD83 glycosylation pattern and reduces its membrane expression. Yeast two-hybrid screening, co-immunoprecipitation, co-localization, mutagenesis, glycosylation analysis, surface expression assay Biochemical and biophysical research communications Medium 25701785
2017 Crystal structures of GRASP55 GRASP domain in complex with the golgin-45 C-terminal peptide (1.33 Å resolution) reveal that golgin-45 binds the canonical PDZ-peptide groove of PDZ1 and also contacts PDZ2; mutagenesis confirms two binding sites are required for stable complex formation; a unique zinc finger structure is present in the complex. X-ray crystallography, mutagenesis, biochemical complex formation assay The Journal of biological chemistry High 28049725
2017 In germ cells, GRASP55 interacts with JAM-C and JAM-B via PDZ-mediated interactions, inducing a conformational change in GRASP55; Gorasp2-/- mice show spermatogenesis defects including impaired acrosome formation, altered JAM-C polarized localization, and disturbed Golgi morphology in spermatocytes; a pharmacophore-based inhibitor (Graspin) disrupting PDZ interactions of GRASP55 with JAMs phenocopies these defects. Proteomic interaction identification, crystal structures of GRASP55-JAM complexes, Gorasp2 knockout mouse phenotyping, pharmacological inhibition PLoS genetics High 28617811
2017 CRISPR/Cas9 double knockout of GRASP55 and GRASP65 disperses Golgi stacks into single cisternae and tubulovesicular structures, accelerates protein trafficking, and impairs accurate glycosylation of proteins and lipids, demonstrating a critical role for GRASPs in maintaining stacked Golgi structure required for accurate posttranslational modifications. CRISPR/Cas9 knockout (single and double), electron microscopy, protein trafficking assay, glycan analysis Molecular biology of the cell High 28814501
2018 Under growth conditions, GRASP55 is O-GlcNAcylated by OGT at the Golgi; glucose deprivation reduces GRASP55 O-GlcNAcylation, causing GRASP55 to redistribute from the Golgi to puncta co-localizing with autophagosomes and late endosomes/lysosomes; de-O-GlcNAcylated GRASP55 interacts with LC3-II on autophagosomes and LAMP2 on lysosomes, functioning as a tether to promote autophagosome-lysosome fusion; O-GlcNAcylation-deficient GRASP55 mutant accelerates autophagic flux. O-GlcNAcylation assay, live-cell imaging, co-immunoprecipitation, GRASP55 KD/KO with autophagic flux assay, expression of O-GlcNAcylation-deficient mutant Developmental cell High 29689198
2019 GRASP55 facilitates autophagosome-lysosome fusion by physically linking autophagosomes (via LC3) and lysosomes (via LAMP2), and also interacts with BECN1 to facilitate assembly and membrane association of the PtdIns3K UVRAG complex during amino acid starvation. Co-immunoprecipitation, GRASP55 depletion with LC3-II/p62 western blot, autophagic flux assay, BECN1 interaction assay Autophagy High 30894053
2019 GRASP55-/- macrophages are defective in mature IL-1β secretion and accumulate it as intracellular aggregates; GRASP55 knockout also impairs the IRE1α branch of the unfolded protein response, and IRE1α inhibition similarly impairs mIL-1β secretion, placing GRASP55 and IRE1α in the same pathway controlling IL-1β unconventional secretion. GRASP55 knockout mouse macrophages, IL-1β secretion assay, aggregate detection, IRE1α pathway analysis Developmental cell High 30880003
2019 SIRT2 interacts with GRASP55 during mitosis when GRASP55 is highly acetylated at K50; SIRT2 depletion causes Golgi fragmentation and impairs post-mitotic Golgi reassembly; expression of acetylation-deficient K50R GRASP55 (but not acetylation-mimetic K50Q) in double-KO cells rescues Golgi structure, demonstrating SIRT2-mediated deacetylation of GRASP55 K50 promotes Golgi reassembly. Co-immunoprecipitation, SIRT2 KD, GRASP55/GRASP65 double-KO complementation with K50R/K50Q mutants, Golgi morphology assay, self-interaction assay Journal of cell science High 31604796
2020 GRASP55 depletion disrupts Golgi ribbon lateral connectivity when depleted chronically but not acutely; acute double depletion of GRASP55 and GRASP65 causes loss of vesicle tethering proteins GM130, p115, and Golgin-45 from the Golgi and compromises ribbon linking; neither GRASP alone is required for maintaining Golgi stacking or de novo stacked cisternae assembly after mitosis. Auxin-inducible degron rapid degradation system, live-cell imaging, immunofluorescence, electron microscopy The Journal of cell biology High 33301566
2020 GRASP55 inactivation in mice reduces whole-body fat mass through impaired intestinal fat absorption; mechanistically, GRASP55 participates in Golgi-mediated lipid droplet targeting of lipases ATGL and MGL, required for sustained lipid supply for chylomicron assembly and secretion; GRASP55 deficiency leads to reduced chylomicron secretion and abnormally large lipid droplets in intestinal epithelial cells. Grasp55-/- mouse phenotyping, lipid absorption assays, lipase localization/fractionation, chylomicron secretion assay, Golgi fractionation Nature communications High 32184397
2020 PKCα directly phosphorylates GRASP55, and elevated intracellular Ca2+ (induced by thapsigargin) causes Golgi fragmentation through PKCα activation and GRASP55 phosphorylation; this signaling axis (Ca2+ → PKCα → GRASP55 phosphorylation → Golgi fragmentation) is also activated by PMA and histamine. In vitro kinase assay, pharmacological PKCα activation/inhibition, Ca2+ manipulation, Golgi morphology quantification iScience High 32179476
2021 mTORC1 directly phosphorylates GRASP55 to maintain its Golgi localization; inhibition of mTORC1 causes GRASP55 dephosphorylation and relocalization to unconventional secretion compartments, enabling secretion of numerous cargo proteins including MMP2; this mTORC1-GRASP55 axis acts as the integration point in stress signaling upstream of unconventional protein secretion (UPS). In vitro mTORC1 kinase assay, phospho-site mapping, live-cell imaging of GRASP55 relocalization, proteomic secretome analysis upon mTORC1 inhibition Molecular cell High 34245671
2021 GRASP55 directs the compartmentalized localization of key glycosphingolipid (GSL) biosynthesis enzymes in the trans-Golgi by binding to these enzymes and preventing their entry into COPI-based retrograde transport vesicles; loss of GRASP55 causes these enzymes to relocate to cis-Golgi, altering flux through GSL metabolic branch points. GRASP55 KO cells, Co-IP of GRASP55 with GSL enzymes, COPI vesicle budding assay, lipidomics, enzyme localization by immunofluorescence The EMBO journal High 34516001
2021 GRASP55 loss enhances LC3 puncta formation, indicating GRASP55 restricts early autophagosome formation; proximity-dependent biotinylation (BioID) identifies a GRASP55 proximal interactome associated with the ER-Golgi interface; both starvation and GRASP55 loss cause coalescence of early secretory pathway markers. GRASP55 KO, LC3 puncta quantification, BioID proximity labeling proteomics, immunofluorescence of ER-Golgi markers Biology open Medium 34533192
2022 GRASP55 facilitates unconventional secretion of mutant huntingtin (Htt-Q74) by two mechanisms: (1) tethering autophagosomes to lysosomes to promote autophagosome maturation and subsequent lysosomal secretion, and (2) stabilizing p23/TMED10, a channel for translocation of cytoplasmic proteins into the ER-Golgi intermediate compartment; GRASP55 KO inhibits Htt secretion and enhances Htt aggregation and toxicity. GRASP55 KO, secretion assay, co-immunoprecipitation (GRASP55-p23/TMED10), autophagosome-lysosome fusion assay, secretomic proteomics The Journal of biological chemistry High 35780830
2024 GORASP2 localizes to the surface of autophagosomes during glucose starvation and promotes phagophore closure by regulating the association between VPS4A and the ESCRT-III component CHMP2A; GORASP2 also controls RAB7A activity by modulating its GEF complex (MON1A-CCZ1), impacting RAB7A interaction with the HOPS complex and assembly of STX17-SNAP29-VAMP8 and YKT6-SNAP29-STX7 SNARE complexes for autophagosome-lysosome fusion. Super-resolution microscopy (SIM), GORASP2 depletion, phagophore closure assay (proteinase K protection), ESCRT/VPS4A association assay, RAB7A-GEF complex assay, SNARE complex co-IP Autophagy High 39056394
2024 GRASP55 interacts with the COPII cargo receptor components and Golgi stacking function at the ER-Golgi interface for Cx36; specifically, the PDZ binding motif 'SAYV' of Cx36 mediates an interaction with GRASP55 that stabilizes Cx36 in the Golgi, opposing the COPII-mediated export from the ER. siRNA knockdown, BioID screen, co-immunoprecipitation, Cx36 trafficking assay in HEK293T cells, overexpression Cellular and molecular life sciences Medium 39395036
2025 GRASP55 depletion results in missorting and secretion of the lysosomal enzyme HEXA (beta-hexosaminidase A), reduced M6P modification of HEXA (via reduced GNPTAB expression), decreased complex formation between HEXA and M6P receptors, and decreased intracellular mature HEXA enzymatic activity. GRASP55 KO, secretomic proteomics, HEXA trafficking/processing assays, M6P receptor co-immunoprecipitation, GNPTAB expression analysis Molecular biology of the cell High 39841559
2025 GRASP55 binds and maintains the COPI adaptor GOLPH3 at the Golgi, thereby controlling the Golgi localization and stability of LYSET and GNPTAB required for M6P tagging of lysosomal enzymes; GRASP55 loss leads to lysosomal enzyme missorting, lysosomal dysfunction, and disruption of lysosomal mTORC1 signaling (reduced TFEB/TFE3 phosphorylation) while sparing non-lysosomal mTORC1 targets. GRASP55 KO, co-immunoprecipitation (GRASP55-GOLPH3), LYSET/GNPTAB stability assay, lysosome function assays, mTORC1 substrate phosphorylation assay EMBO reports High 41991615
2025 CDK1 phosphorylates GRASP55 at the T225 site; CDK1 downregulation reverses GRASP55 T225 phosphorylation and attenuates Golgi apparatus stress, neuronal apoptosis, and inflammatory responses after intracerebral hemorrhage; mutation of GRASP55 T225 abolishes CDK1-mediated exacerbation of Golgi stress and neuronal damage. In vitro kinase assay (CDK1 phosphorylation of GRASP55 T225), site-directed mutagenesis, CDK1 knockdown in ICH rat model and cell lines, Golgi stress and apoptosis readouts Cellular signalling Medium 40288664
2025 GRASP55 (but not GRASP65) is recruited to late phagosomes in dendritic cells and is essential for sorting MHC-I and MHC-II molecules from the endocytic system to the plasma membrane, enabling exogenous antigen presentation; GRASP55-deficient bone-marrow-derived DCs show significantly impaired antigen presentation. GRASP55 KO (CRISPR), antigen presentation assay with soluble/bead/bacterial antigens, phagosome recruitment imaging, MHC trafficking assay Cell reports High 39955774

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 GRASP55, a second mammalian GRASP protein involved in the stacking of Golgi cisternae in a cell-free system. The EMBO journal 281 10487747
2001 A GRASP55-rab2 effector complex linking Golgi structure to membrane traffic. The Journal of cell biology 193 11739401
2010 GRASP55 and GRASP65 play complementary and essential roles in Golgi cisternal stacking. The Journal of cell biology 164 20083603
2013 Regulation of protein glycosylation and sorting by the Golgi matrix proteins GRASP55/65. Nature communications 152 23552074
2008 GRASP55 regulates Golgi ribbon formation. Molecular biology of the cell 127 18434598
2018 GRASP55 Senses Glucose Deprivation through O-GlcNAcylation to Promote Autophagosome-Lysosome Fusion. Developmental cell 121 29689198
2017 Knockout of the Golgi stacking proteins GRASP55 and GRASP65 impairs Golgi structure and function. Molecular biology of the cell 94 28814501
2000 Transmembrane transforming growth factor-alpha tethers to the PDZ domain-containing, Golgi membrane-associated protein p59/GRASP55. The EMBO journal 94 11101516
2008 The role of GRASP55 in Golgi fragmentation and entry of cells into mitosis. Molecular biology of the cell 75 18385516
2019 GORASP2/GRASP55 collaborates with the PtdIns3K UVRAG complex to facilitate autophagosome-lysosome fusion. Autophagy 61 30894053
2009 GRASP65 and GRASP55 sequentially promote the transport of C-terminal valine-bearing cargos to and through the Golgi complex. The Journal of biological chemistry 60 19840934
2021 An mTORC1-GRASP55 signaling axis controls unconventional secretion to reshape the extracellular proteome upon stress. Molecular cell 59 34245671
2020 Nonredundant Roles of GRASP55 and GRASP65 in the Golgi Apparatus and Beyond. Trends in biochemical sciences 58 32893104
2021 Rapid degradation of GRASP55 and GRASP65 reveals their immediate impact on the Golgi structure. The Journal of cell biology 47 33301566
2019 GRASP55 and UPR Control Interleukin-1β Aggregation and Secretion. Developmental cell 43 30880003
2021 GRASP55 regulates intra-Golgi localization of glycosylation enzymes to control glycosphingolipid biosynthesis. The EMBO journal 42 34516001
2013 Structural insight into Golgi membrane stacking by GRASP65 and GRASP55 proteins. The Journal of biological chemistry 42 23940043
2022 GRASP55 regulates the unconventional secretion and aggregation of mutant huntingtin. The Journal of biological chemistry 39 35780830
2020 Cytosolic Ca2+ Modulates Golgi Structure Through PKCα-Mediated GRASP55 Phosphorylation. iScience 34 32179476
2017 Structural Basis for the Interaction between Golgi Reassembly-stacking Protein GRASP55 and Golgin45. The Journal of biological chemistry 32 28049725
2017 Genetic, structural, and chemical insights into the dual function of GRASP55 in germ cell Golgi remodeling and JAM-C polarized localization during spermatogenesis. PLoS genetics 31 28617811
2018 The Golgi stacking protein GORASP2/GRASP55 serves as an energy sensor to promote autophagosome maturation under glucose starvation. Autophagy 26 29973119
2020 Grasp55-/- mice display impaired fat absorption and resistance to high-fat diet-induced obesity. Nature communications 22 32184397
2019 Unconventional secretion factor GRASP55 is increased by pharmacological unfolded protein response inducers in neurons. Scientific reports 19 30733486
2018 GRASP55 facilitates autophagosome maturation under glucose deprivation. Molecular & cellular oncology 19 30250930
2015 CD83 and GRASP55 interact in human dendritic cells. Biochemical and biophysical research communications 19 25701785
1994 Entire nucleotide sequence for Bacillus brevis Nagano Grs2 gene encoding gramicidin S synthetase 2: a multifunctional peptide synthetase. Journal of biochemistry 19 7822255
2020 GRASP55: A Multifunctional Protein. Current protein & peptide science 12 32067616
2019 SIRT2 deacetylates GRASP55 to facilitate post-mitotic Golgi assembly. Journal of cell science 12 31604796
2021 GRASP55 restricts early-stage autophagy and regulates spatial organization of the early secretory network. Biology open 9 34533192
2015 The chemical chaperone sodium 4-phenylbutyrate improves the secretion of the protein CA267T mutant in CHO-K1 cells trough the GRASP55 pathway. Cell & bioscience 9 26457178
2005 Purification and functional interactions of GRASP55 with Rab2. Methods in enzymology 8 16473605
2024 GORASP2 promotes phagophore closure and autophagosome maturation into autolysosomes. Autophagy 7 39056394
2020 Nucleation-dependent amyloid fibrillation of human GRASP55 in aqueous solution. European biophysics journal : EBJ 7 31915857
2019 Exploring structural aspects of the human Golgi matrix protein GRASP55 in solution. International journal of biological macromolecules 7 31102680
2023 The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin. Cell communication and signaling : CCS 5 37798768
2020 GRASP55 Is Dispensable for Normal Hematopoiesis but Necessary for Myc-Dependent Leukemic Growth. Journal of immunology (Baltimore, Md. : 1950) 5 32229537
2025 GRASP55 regulates sorting and maturation of the lysosomal enzyme β-hexosaminidase A. Molecular biology of the cell 3 39841559
2025 Dendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules. Cell reports 3 39955774
2025 Targeting CDK1 inhibits Golgi apparatus stress-mediated neuroinflammation and neuronal apoptosis after intracerebral hemorrhage by modulating GRASP55 phosphorylation. Cellular signalling 2 40288664
2024 Myristoylated GRASP55 dimerizes in the presence of model membranes. Journal of biomolecular structure & dynamics 2 38361284
2024 Regulation of Cx36 trafficking through the early secretory pathway by COPII cargo receptors and Grasp55. Cellular and molecular life sciences : CMLS 2 39395036
2023 Identification and Characterization of GRASP55 O-GlcNAcylation. Methods in molecular biology (Clifton, N.J.) 2 36512248
2026 GRASP55 maintains lysosome function by controlling sorting of lysosomal enzymes at the Golgi. EMBO reports 0 41991615
2025 The Golgi Stacking Protein GORASP2 Regulates Mouse Primordial Follicle Activation by Suppressing the Autophagy Lysosome Pathway via RAP1 Competing With mTOR for RAPTOR Binding. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 40522147
2024 GRASP55 Regulates Sorting and Maturation of the Lysosomal Enzyme β-Hexosaminidase A. bioRxiv : the preprint server for biology 0 39464054

Missed literature

Know a paper Affinage missed for GORASP2? Flag it for the maintainers and the community.

No submissions yet.