Affinage

GORASP2

Golgi reassembly-stacking protein 2 · UniProt Q9H8Y8

Length
452 aa
Mass
47.1 kDa
Annotated
2026-04-28
46 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GORASP2/GRASP55 is a myristoylated peripheral Golgi membrane protein that organizes Golgi architecture, controls cargo-specific trafficking and glycosylation, and mediates autophagosome–lysosome fusion under nutrient stress. Its N-terminal tandem PDZ (GRASP) domain forms trans-oligomers that tether adjacent cisternae into stacks and link stacks into the Golgi ribbon, an activity negatively regulated by mitotic and stress-responsive phosphorylation (ERK, CDK1 at T225/T249, PKCα, mTORC1) and acetylation at K50 (reversed by SIRT2), and positively maintained by O-GlcNAcylation (PMID:10487747, PMID:20083603, PMID:18434598, PMID:29689198, PMID:31604796). GRASP55 functions as a PDZ-dependent sorting receptor for C-terminal valine-bearing transmembrane cargoes (TGF-α, Frizzled4, CD83, JAM-C, Cx36), retains glycosphingolipid biosynthesis enzymes in the trans-Golgi by excluding them from COPI retrograde vesicles, and maintains lysosomal enzyme mannose 6-phosphate tagging by stabilizing GNPTAB and GOLPH3 at the Golgi (PMID:11101516, PMID:19840934, PMID:34516001, PMID:41991615). Upon glucose deprivation or mTORC1 inhibition, de-modified GRASP55 relocalizes to autophagosome–lysosome interfaces where it bridges LC3-II and LAMP2 to promote fusion, regulates phagophore closure via ESCRT-III/VPS4A, facilitates RAB7A–HOPS–SNARE complex assembly, and drives unconventional secretion of cytoplasmic proteins including mutant huntingtin (PMID:29689198, PMID:39056394, PMID:35780830, PMID:34245671).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Establishing GRASP55 as a Golgi-stacking factor resolved the question of whether a second GRASP-family protein existed and whether it contributed to cisternal stacking independently of GRASP65.

    Evidence Cell-free Golgi stacking assay with recombinant GRASP55 addition and antibody inhibition, cryo-EM localization to medial-Golgi

    PMID:10487747

    Open questions at the time
    • In vivo requirement for stacking not yet shown
    • Relationship to GRASP65 function undefined
    • Membrane-attachment mechanism incompletely characterized
  2. 2000 High

    Identifying GRASP55 as a PDZ-domain cargo receptor for TGF-α established a trafficking function distinct from structural stacking, showing that GRASP55 directly recognizes C-terminal valine motifs of transmembrane cargo.

    Evidence Co-IP, yeast two-hybrid, mutagenesis of TGF-α C-terminus, surface expression assay

    PMID:11101516

    Open questions at the time
    • Generality of C-terminal valine recognition to other cargoes unknown
    • Whether cargo binding and stacking are separable functions unclear
  3. 2001 High

    Discovering the GRASP55–golgin-45–Rab2 complex showed how GRASP55 is anchored functionally at the medial-Golgi and connected Rab GTPase signaling to Golgi structure and secretory transport.

    Evidence Reciprocal Co-IP, yeast two-hybrid, golgin-45 depletion with transport block readout

    PMID:11739401

    Open questions at the time
    • Stoichiometry and assembly order of the complex unknown
    • Whether Rab2 GTP hydrolysis regulates the interaction untested
  4. 2008 High

    Demonstrating that MEK1/ERK and CDK1 phosphorylate GRASP55 at T225/T249 to fragment the Golgi at mitosis established the key regulatory switch controlling GRASP55 oligomerization during cell division.

    Evidence Phospho-peptide mapping, phosphomimetic mutagenesis, cell-free Golgi fragmentation assay, cell cycle analysis with siRNA

    PMID:18385516 PMID:18434598

    Open questions at the time
    • Identity of the phosphatase(s) responsible for post-mitotic dephosphorylation unknown
    • Whether ERK and CDK1 act sequentially or redundantly on the same sites unresolved
  5. 2010 High

    Quantitative EM analysis of single and combined GRASP55/GRASP65 depletion resolved the relative contributions of each paralog and showed that GRASP55 oligomerization through its N-terminal GRASP domain is negatively regulated by C-terminal phosphorylation.

    Evidence siRNA knockdown of one or both GRASPs, EM-based cisternae-per-stack quantification, phosphomutant rescue

    PMID:20083603

    Open questions at the time
    • Exact phosphorylation sites controlling oligomerization not fully mapped
    • Trans-oligomer versus cis-oligomer contributions not distinguished
  6. 2013 High

    Crystal structures of the GRASP domain revealed the precise molecular basis of trans-oligomerization — PDZ2-mediated dimerization plus C-terminal tail insertion into PDZ1 of an adjacent dimer — and separate work showed that GRASPs slow cargo transit to ensure complete glycosylation.

    Evidence X-ray crystallography with mutagenesis validation; siRNA KD with glycan mass spectrometry and transport kinetics

    PMID:23552074 PMID:23940043

    Open questions at the time
    • How cargo-binding and oligomerization are coordinated structurally unresolved
    • Whether glycosylation defects are direct or secondary to accelerated transit debated
  7. 2017 High

    High-resolution structures of GRASP55 with golgin-45 and JAM-C peptides, combined with GRASP55-knockout mouse spermatogenesis defects, demonstrated that PDZ-mediated interactions serve both structural (golgin-45 tethering) and cargo-sorting (JAM-C polarization, acrosome biogenesis) functions in vivo.

    Evidence Crystal structures (1.33 Å GRASP55–golgin-45; GRASP55–JAM-C), Gorasp2 KO mouse with acrosome/spermatid phenotype, Graspin inhibitor

    PMID:28049725 PMID:28617811

    Open questions at the time
    • Whether the Graspin inhibitor affects stacking and cargo sorting equally unknown
    • In vivo Golgi morphology in KO testis not fully characterized
  8. 2017 High

    CRISPR double knockout of both GRASPs confirmed they are essential for maintaining stacked Golgi architecture and accurate glycosylation, providing the definitive genetic evidence that superseded RNAi-based studies.

    Evidence CRISPR/Cas9 KO, EM morphology, transport assay, glycan analysis

    PMID:28814501

    Open questions at the time
    • Whether individual GRASP KOs are truly dispensable or compensated is debated
    • Long-term adaptive changes in KO lines not controlled for
  9. 2018 High

    The discovery that O-GlcNAcylation by OGT retains GRASP55 at the Golgi while glucose deprivation triggers its relocalization to autophagosome–lysosome membranes — where it bridges LC3-II and LAMP2 — revealed a nutrient-sensing switch repurposing a Golgi structural protein for autophagy.

    Evidence O-GlcNAc modification assay, Co-IP of GRASP55 with LC3-II and LAMP2, autophagic flux assay, O-GlcNAcylation-deficient mutant

    PMID:29689198

    Open questions at the time
    • Specific O-GlcNAcylation sites mediating Golgi retention not fully mapped
    • Whether GRASP55 relocalization requires de novo membrane targeting signals unknown
  10. 2019 High

    Multiple studies in 2019 expanded GRASP55's roles: it interacts with BECN1 to promote PtdIns3K-UVRAG complex assembly during starvation-induced autophagy, is required for unconventional secretion of mature IL-1β in macrophages, and is regulated by SIRT2-mediated deacetylation at K50 to control Golgi reassembly after mitosis.

    Evidence Co-IP of GRASP55-BECN1; GRASP55 KO macrophages with IL-1β secretion assay; K50R/K50Q mutagenesis in double-KO rescue with self-interaction assay

    PMID:30880003 PMID:30894053 PMID:31604796

    Open questions at the time
    • Whether BECN1 interaction and IL-1β secretion use the same GRASP55 pool unclear
    • SIRT2 KO effect on Golgi in vivo not tested
    • Whether acetylation and phosphorylation are coordinated at mitosis unknown
  11. 2020 High

    Two studies broadened GRASP55 regulation and physiology: PKCα was identified as a Ca²⁺-responsive kinase phosphorylating GRASP55 to fragment the Golgi, and GRASP55 KO mice revealed a role in intestinal fat absorption through Golgi-mediated lipase targeting required for chylomicron assembly.

    Evidence PKCα pharmacological activation/inhibition with Golgi morphology readout; Grasp55 KO mouse with lipid absorption, chylomicron secretion, and lipase localization assays

    PMID:32179476 PMID:32184397

    Open questions at the time
    • Direct PKCα phosphorylation sites on GRASP55 not mapped in vitro
    • Whether lipid absorption defect is Golgi-structure-dependent or cargo-sorting-dependent unclear
  12. 2021 High

    Three advances in 2021 refined the model: mTORC1 was shown to directly phosphorylate GRASP55 to maintain Golgi localization (with inhibition triggering unconventional secretion), acute degron-mediated depletion revealed GRASP55 is dispensable for stacks but required chronically for ribbon linking, and GRASP55 was shown to retain glycosphingolipid enzymes in the trans-Golgi by excluding them from COPI vesicles.

    Evidence In vitro mTORC1 kinase assay with secretome proteomics; auxin-inducible degron with EM; GRASP55 KO with COPI vesicle budding assay and lipidomics

    PMID:33301566 PMID:34245671 PMID:34516001

    Open questions at the time
    • mTORC1 phosphorylation sites mediating Golgi retention versus UPS not individually mapped
    • Whether chronic ribbon-linking defect reflects secondary loss of tethering factors (golgin-45, GM130) rather than direct GRASP55 function
  13. 2022 High

    GRASP55 was shown to facilitate unconventional secretion of aggregation-prone mutant huntingtin by stabilizing TMED10/p23 as a translocation channel and tethering autophagosomes to lysosomes, establishing GRASP55 as a general unconventional secretion factor.

    Evidence GRASP55 KO, Co-IP of GRASP55–TMED10, Htt-Q74 secretion and aggregation assay, secretomics

    PMID:35780830

    Open questions at the time
    • Whether GRASP55 directly stabilizes TMED10 or acts indirectly via Golgi structure unresolved
    • In vivo relevance to neurodegeneration not tested
  14. 2024 High

    Detailed dissection of GRASP55's autophagy role revealed it controls phagophore closure via ESCRT-III (CHMP2A)–VPS4A and promotes RAB7A activation through the MON1A-CCZ1 GEF, enabling HOPS tethering and dual SNARE complex assembly (STX17-SNAP29-VAMP8; YKT6-SNAP29-STX7), providing the most complete mechanistic picture of GRASP55 in autophagosome maturation.

    Evidence Super-resolution microscopy, GORASP2 depletion, Co-IP of VPS4A–CHMP2A, MON1A–CCZ1–RAB7A, HOPS, and SNARE complexes

    PMID:39056394

    Open questions at the time
    • Whether GRASP55 directly binds ESCRT-III components or acts through an adaptor unknown
    • Relative importance of phagophore closure versus fusion functions not separated
  15. 2025 High

    Recent work established that GRASP55 maintains lysosomal enzyme sorting by stabilizing GOLPH3 and GNPTAB at the Golgi to ensure mannose 6-phosphate tagging, and independently showed GRASP55 is required for MHC-I/II antigen presentation in dendritic cells, revealing new physiological roles.

    Evidence GRASP55 KO with secretomics, Co-IP of GRASP55–GOLPH3, M6P tagging and lysosomal function assays; GRASP55-deficient BMDCs with antigen presentation assay

    PMID:39841559 PMID:39955774 PMID:41991615

    Open questions at the time
    • Whether lysosomal dysfunction feeds back to alter GRASP55-dependent autophagy unknown
    • Mechanism of GRASP55 recruitment to late phagosomes in DCs uncharacterized
    • Whether antigen presentation defect is due to MHC trafficking or broader Golgi dysfunction unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how GRASP55 distributes between its Golgi-structural, cargo-sorting, autophagy, and unconventional-secretion functions in a single cell; the identities of phosphatases that reverse mitotic and mTORC1-mediated phosphorylation; and whether GRASP55 dysfunction contributes to human disease.
  • No phosphatase identified for post-mitotic GRASP55 dephosphorylation
  • No human Mendelian disease linked to GORASP2 mutations
  • No structural model of full-length GRASP55 including the SPR domain

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 3
Localization
GO:0005794 Golgi apparatus 8 GO:0005764 lysosome 4 GO:0031410 cytoplasmic vesicle 4 GO:0005829 cytosol 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 7 R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-1640170 Cell Cycle 4 R-HSA-9612973 Autophagy 4 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2
Partners
BLZF1GNPTABGOLPH3LAMP2MAP1LC3BRAB2ASIRT2TMED10
Complex memberships
GRASP55–golgin-45–Rab2 complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 GRASP55 (GORASP2) is a 55 kDa peripheral Golgi membrane protein localized to medial-Golgi cisternae that is required for stacking of Golgi cisternae in a cell-free system; recombinant GRASP55 and antibodies to it block cisternal stacking in vitro. Cell-free Golgi stacking assay, cryo-electron microscopy, recombinant protein addition/antibody inhibition The EMBO journal High 10487747
2001 GRASP55 forms a complex with the coiled-coil protein golgin-45 and the GTP-bound form of Rab2 GTPase on medial-Golgi; this rab2 effector complex is essential for secretory protein transport and Golgi structure, as depletion of golgin-45 disrupts the Golgi and blocks transport. Co-immunoprecipitation, yeast two-hybrid, protein depletion with transport assay The Journal of cell biology High 11739401
2000 GRASP55 (p59) is myristoylated and palmitoylated, associates with the Golgi, and its first PDZ domain directly interacts with the C-terminus of transmembrane TGF-alpha; C-terminal mutations of TGF-alpha that abolish this interaction strongly impair TGF-alpha cell surface expression. Protein purification, co-immunoprecipitation, yeast two-hybrid, mutagenesis, surface expression assay The EMBO journal High 11101516
2008 GRASP55 mediates Golgi ribbon formation and linking of Golgi stacks; MEK1/ERK phosphorylates GRASP55 at G2/M to unlink the Golgi ribbon. Depletion of GRASP55 produces a fragmented Golgi similar to G2-arrested cells and suppresses the MEK1 requirement for G2/M transition. Phosphomimetic aspartic acid substitutions in GRASP55 are sufficient to unlink the Golgi ribbon. siRNA knockdown, phosphomimetic mutagenesis (gene replacement assay), cell cycle analysis, Golgi morphology imaging Molecular biology of the cell High 18434598
2008 GRASP55 is mitotically phosphorylated at threonine 225 and 249; phosphorylation at these sites is required for Golgi fragmentation and cell entry into mitosis. Wild-type peptides containing T225/T249 inhibit mitotic Golgi fragmentation, while phosphomimetic T225E/T249E peptides do not, suggesting phosphorylation releases a bound partner needed for fragmentation. Phospho-peptide mapping, cell-free Golgi fragmentation assay, peptide inhibition with wild-type and phosphomimetic mutants Molecular biology of the cell High 18385516
2010 GRASP55 stacks Golgi membranes by forming oligomers through its N-terminal GRASP domain; phosphorylation within the C-terminal serine/proline-rich domain negatively regulates this oligomerization. siRNA depletion of GRASP55 or GRASP65 individually reduces cisternae per stack, while combined depletion disassembles the entire stack. Non-phosphorylatable GRASP55 mutants enhance stacking in interphase and inhibit mitotic disassembly. siRNA knockdown, phosphomutant expression, Golgi morphology quantification by EM, oligomerization assay The Journal of cell biology High 20083603
2009 GRASP55 PDZ domains directly bind C-terminal valine-bearing cargo receptors (CD8alpha, Frizzled4); both GRASP55 and GRASP65 are required sequentially for efficient transport of these receptors to and through the Golgi complex. Direct binding assay (PDZ-peptide interaction), siRNA knockdown, cargo transport assay The Journal of biological chemistry High 19840934
2013 Crystal structures of the GRASP domain of GRASP55 reveal that it forms a dimer in which PDZ2 binding pockets face each other and dimers are further connected by C-terminal tail insertion into PDZ1 of an adjacent dimer; biochemical analysis confirms both contacts are needed for GRASP-mediated Golgi stacking. X-ray crystallography, biochemical mutagenesis, Golgi stacking assay The Journal of biological chemistry High 23940043
2013 Knockdown of GRASP55 and/or GRASP65 accelerates protein trafficking through Golgi membranes and has striking negative effects on protein glycosylation and sorting; GRASPs act as negative regulators of exocytic transport to ensure complete glycosylation. siRNA knockdown, glycan mass spectrometry, transport kinetics assay, sorting assay Nature communications High 23552074
2017 Crystal structure of GRASP55 GRASP domain in complex with golgin-45 C-terminal peptide (1.33 Å) reveals that golgin-45 engages both PDZ1 and PDZ2 domains via a conserved PDZ-binding motif; a unique zinc finger structure is present in the complex. Mutagenesis confirms two binding sites are required for stable complex formation. X-ray crystallography, mutagenesis, Co-immunoprecipitation The Journal of biological chemistry High 28049725
2017 GRASP55 (Gorasp2) interacts via PDZ-mediated interactions with junctional adhesion molecules JAM-C and JAM-B in developing germ cells; Gorasp2-knockout mice show defective acrosome formation and loss of polarized JAM-C localization in spermatids; crystal structures of GRASP55 with JAM-C or JAM-B reveal a conformational change in GRASP55 upon binding. Proteomics/mass spectrometry, knockout mouse, crystal structure, PDZ inhibitor (Graspin) treatment PLoS genetics High 28617811
2017 CRISPR/Cas9 double knockout of GRASP55 and GRASP65 disperses the Golgi stack into single cisternae and tubulovesicular structures, accelerates protein trafficking, and impairs glycosylation of proteins and lipids, demonstrating that GRASPs are critical for stacked Golgi structure and accurate post-translational modifications. CRISPR/Cas9 knockout, EM morphology, transport 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 O-GlcNAcylation, causing GRASP55 to relocalize from the Golgi to the autophagosome-lysosome interface where it interacts with LC3-II on autophagosomes and LAMP2 on lysosomes, acting as a tether to facilitate autophagosome-lysosome fusion. O-GlcNAcylation-deficient GRASP55 mutant accelerates autophagic flux. O-GlcNAc modification assay, co-immunoprecipitation, live imaging, siRNA knockdown, autophagic flux assay (LC3-II/SQSTM1 levels), O-GlcNAcylation-deficient mutant expression Developmental cell High 29689198
2019 GRASP55 facilitates autophagosome-lysosome fusion by physically linking autophagosomes (via LC3 interaction) and lysosomes (via LAMP2 interaction), and also interacts with BECN1 to facilitate assembly and membrane association of the PtdIns3K UVRAG complex during amino acid starvation. Co-immunoprecipitation (GRASP55-LC3, GRASP55-LAMP2, GRASP55-BECN1), siRNA depletion with autophagic flux readout, electron microscopy Autophagy High 30894053
2019 GRASP55 knockout macrophages are defective in mature IL-1β secretion, retaining it as intracellular aggregates; GRASP55 and IRE1α activity are required to keep mIL-1β in a secretion-competent form, while PERK controls caspase-1-mediated conversion of pro-IL-1β to mIL-1β. GRASP55 knockout mouse macrophages, IRE1α/PERK inhibition, IL-1β secretion assay, aggregate detection Developmental cell High 30880003
2019 SIRT2 deacetylase interacts with GRASP55 during mitosis when GRASP55 is highly acetylated at K50; SIRT2 depletion causes Golgi fragmentation; expression of acetylation-deficient K50R GRASP55 (but not acetylation-mimetic K50Q) rescues Golgi structure and post-mitotic Golgi reassembly in double-KO cells, and K50R shows higher self-interaction efficiency. Co-immunoprecipitation, acetylation-site mutagenesis, Golgi rescue assay in double-KO cells, self-interaction assay Journal of cell science High 31604796
2020 Cytosolic Ca2+ elevation (via thapsigargin) induces Golgi fragmentation through PKCα-mediated phosphorylation of GRASP55; other PKCα activators (PMA, histamine) similarly modulate Golgi structure. Pharmacological Ca2+ elevation, PKCα activation/inhibition, phosphorylation assay, Golgi morphology imaging iScience Medium 32179476
2020 Genetic inactivation of GRASP55 in mice reduces whole-body fat mass via impaired intestinal fat absorption; mechanistically, GRASP55 participates in Golgi-mediated lipid droplet targeting of lipases ATGL and MGL, required for chylomicron assembly and secretion. Deficiency leads to reduced chylomicron secretion and abnormally large lipid droplets in intestinal epithelial cells. Grasp55 knockout mouse, lipid absorption assay, chylomicron secretion assay, lipase localization by imaging/fractionation Nature communications High 32184397
2021 mTORC1 directly phosphorylates GRASP55 to maintain its Golgi localization. mTORC1 inhibition causes GRASP55 dephosphorylation and relocalization to unconventional secretion (UPS) compartments, driving secretion of numerous cargo proteins including MMP2, reshaping the cellular secretome under stress. In vitro mTORC1 kinase assay, phospho-proteomics, mTOR inhibitor treatment, GRASP55 relocalization imaging, proteomic secretome analysis Molecular cell High 34245671
2021 Acute depletion of GRASP55 (or GRASP65) alone via degron-tag does not affect the Golgi ribbon, but chronic GRASP55 degradation disrupts lateral ribbon connectivity. Acute double depletion of both GRASPs causes loss of vesicle tethering proteins GM130, p115, and Golgin-45 from the Golgi and compromises ribbon linking; neither GRASP is required for maintaining stacks or de novo post-mitotic stack assembly. Auxin-inducible degron (AID) rapid degradation, Golgi morphology by EM, immunofluorescence The Journal of cell biology High 33301566
2021 GRASP55 directs compartmentalized localization of key glycosphingolipid (GSL) biosynthesis enzymes in the trans-Golgi by binding them and preventing their entry into COPI-based retrograde transport vesicles; GRASP55 loss causes enzyme relocation to cis-Golgi and alters GSL biosynthesis flux. GRASP55 genome-edited KO cells, Co-immunoprecipitation, COPI vesicle budding assay, lipidomics, enzyme localization by immunofluorescence The EMBO journal High 34516001
2022 GRASP55 facilitates unconventional secretion of mutant huntingtin (Htt-Q74) by tethering autophagosomes to lysosomes and by stabilizing p23/TMED10, a channel for translocation of cytoplasmic proteins into the ER-Golgi intermediate compartment. GRASP55 KO inhibits Htt-Q74 secretion and enhances its aggregation. GRASP55 KO, co-immunoprecipitation (GRASP55-p23/TMED10), secretion assay, autophagosome-lysosome fusion assay, secretomics The Journal of biological chemistry High 35780830
2015 GRASP55 interacts with CD83 via the C-terminal TELV-motif of CD83 in human dendritic cells; mutation of the TELV-motif disrupts GRASP55 binding, alters CD83 glycosylation pattern, and reduces CD83 membrane expression. Yeast two-hybrid, co-immunoprecipitation, co-localization, mutagenesis, surface expression assay Biochemical and biophysical research communications Medium 25701785
2024 GORASP2 promotes phagophore closure by regulating the association between VPS4A and the ESCRT-III component CHMP2A; it also controls RAB7A activity by modulating its GEF complex (MON1A-CCZ1), thereby enabling RAB7A interaction with the HOPS complex; loss of GORASP2 attenuates assembly of both STX17-SNAP29-VAMP8 and YKT6-SNAP29-STX7 SNARE complexes required for autophagosome-lysosome fusion. Super-resolution microscopy (SIM), GORASP2 depletion, Co-immunoprecipitation (VPS4A-CHMP2A, MON1A-CCZ1-RAB7A, HOPS, SNARE complexes), phagophore closure assay Autophagy High 39056394
2025 CDK1 phosphorylates GRASP55 at T225 in neurons; CDK1 downregulation reduces GRASP55 phosphorylation and attenuates Golgi apparatus stress-mediated neuronal apoptosis and neuroinflammation after intracerebral hemorrhage. Mutation of GRASP55 T225 abolishes CDK1-mediated Golgi stress exacerbation. In vivo ICH rat model, in vitro neuronal model, CDK1 knockdown, phosphosite mutagenesis (T225), Golgi stress markers, apoptosis assay Cellular signalling Medium 40288664
2025 GRASP55 is essential for antigen presentation in dendritic cells; it is recruited to late phagosomes and is required for sorting and trafficking of peptide-loaded MHC-I and MHC-II molecules to the plasma membrane. GRASP55-deficient bone-marrow-derived DCs show significantly impaired exogenous antigen presentation. GRASP55-deficient BMDCs (genetic KO), antigen presentation assay with soluble/bead/bacterial antigens, GRASP55 localization to late phagosomes by imaging Cell reports Medium 39955774
2025 GRASP55 maintains lysosome function by controlling sorting of lysosomal enzymes at the Golgi; it binds and maintains the COPI adaptor GOLPH3 at the Golgi, thereby controlling localization and stability of LYSET and GNPTAB required for mannose 6-phosphate tagging of lysosomal enzymes. GRASP55 loss leads to missorting/secretion of lysosomal enzymes, lysosomal dysfunction, and disrupted lysosomal mTORC1 signaling (reduced TFEB/TFE3 phosphorylation). GRASP55 KO, secretomics, Co-immunoprecipitation (GRASP55-GOLPH3, GOLPH3-LYSET, GOLPH3-GNPTAB), M6P tagging assay, lysosomal function assay, mTORC1 substrate phosphorylation EMBO reports High 41991615
2025 GRASP55 depletion disrupts normal trafficking and processing of the lysosomal enzyme beta-hexosaminidase A (HEXA), causing secretion of immature pro-HEXA and reduced mature enzymatic activity; this is due to reduced GNPTAB expression, leading to decreased M6P modification of HEXA and impaired MPR-dependent lysosomal targeting. GRASP55 KO secretomics, HEXA trafficking/processing assay, M6P modification assay, MPR co-immunoprecipitation, GNPTAB expression analysis Molecular biology of the cell High 39841559
2024 The C-terminal PDZ-binding motif 'SAYV' of Cx36 mediates direct interaction with GRASP55, which stabilizes Cx36 in the Golgi; this is distinct from Sec24-mediated ER export. Overexpression of GRASP55 stabilizes Cx36 in the Golgi. siRNA knockdown, BioID proximity screen, co-immunoprecipitation, overexpression, Cx36 trafficking assay in HEK293T cells Cellular and molecular life sciences Medium 39395036

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 280 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 151 23552074
2008 GRASP55 regulates Golgi ribbon formation. Molecular biology of the cell 125 18434598
2018 GRASP55 Senses Glucose Deprivation through O-GlcNAcylation to Promote Autophagosome-Lysosome Fusion. Developmental cell 121 29689198
2000 Transmembrane transforming growth factor-alpha tethers to the PDZ domain-containing, Golgi membrane-associated protein p59/GRASP55. The EMBO journal 94 11101516
2017 Knockout of the Golgi stacking proteins GRASP55 and GRASP65 impairs Golgi structure and function. Molecular biology of the cell 93 28814501
2008 The role of GRASP55 in Golgi fragmentation and entry of cells into mitosis. Molecular biology of the cell 74 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 56 34245671
2020 Nonredundant Roles of GRASP55 and GRASP65 in the Golgi Apparatus and Beyond. Trends in biochemical sciences 56 32893104
2021 Rapid degradation of GRASP55 and GRASP65 reveals their immediate impact on the Golgi structure. The Journal of cell biology 46 33301566
2019 GRASP55 and UPR Control Interleukin-1β Aggregation and Secretion. Developmental cell 43 30880003
2013 Structural insight into Golgi membrane stacking by GRASP65 and GRASP55 proteins. The Journal of biological chemistry 42 23940043
2021 GRASP55 regulates intra-Golgi localization of glycosylation enzymes to control glycosphingolipid biosynthesis. The EMBO journal 38 34516001
2022 GRASP55 regulates the unconventional secretion and aggregation of mutant huntingtin. The Journal of biological chemistry 37 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 31 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 21 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
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
2024 GORASP2 promotes phagophore closure and autophagosome maturation into autolysosomes. Autophagy 6 39056394
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 Dendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules. Cell reports 3 39955774
2024 Myristoylated GRASP55 dimerizes in the presence of model membranes. Journal of biomolecular structure & dynamics 2 38361284
2023 Identification and Characterization of GRASP55 O-GlcNAcylation. Methods in molecular biology (Clifton, N.J.) 2 36512248
2025 GRASP55 regulates sorting and maturation of the lysosomal enzyme β-hexosaminidase A. Molecular biology of the cell 1 39841559
2025 Targeting CDK1 inhibits Golgi apparatus stress-mediated neuroinflammation and neuronal apoptosis after intracerebral hemorrhage by modulating GRASP55 phosphorylation. Cellular signalling 1 40288664
2024 Regulation of Cx36 trafficking through the early secretory pathway by COPII cargo receptors and Grasp55. Cellular and molecular life sciences : CMLS 1 39395036
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