juxtanuclear quality control compartment

cellstructuremech:juxtanuclear_quality_control_compartment · Inclusion · Inclusion body · Proposed

A cytoplasmic, perinuclear protein-quality-control inclusion characterized in budding yeast, formed by congregation of misfolded-protein deposits near the nuclear envelope and distinct from the intranuclear quality control compartment. [DOI:10.1038/s41556-023-01128-6]

Multi-panel yeast JUNQ reporter characterization. Panels A-C compare wild-type and chaperone-perturbed cells: NES-LuciTs is magenta, the nuclear region is marked in yellow and blue, vacuoles are grey and mitochondria are cyan. Microscopy scale bars in A-C are 1 micrometer. Panels D-E compare static peripheral inclusions in the ssa1/ssa2 double mutant with an HTT/IPOD comparator, not positive wild-type JUNQ. Panels F-H show reporter immunoblots and turnover quantification. FLUORESCENCE · *Saccharomyces cerevisiae BY4741* (`NCBITaxon:1247190`) · Sarah Rolli, Chloe A. Langridge and Emily M. Sontag (2024), Figure 2; CC BY 4.0, via PubMed Central. Unmodified. · CC_BY_4_0 · source: PMC PMC11372896.1 F2 · `DOI:10.3389/fmolb.2024.1427542`

Synonyms: JUNQ

Part of: GO:0005737 — cytoplasm (no local record)

UniProt location names: UniProt Consortium, CC BY 4.0. Reference label and route sources.

Components

Component	Type	Part of / acts on	Grounding	Genes	Essential	Role
heterogeneous JUNQ protein cargo	Other	part of	Reviewed label only (reviewed name; no accession asserted)		UNKNOWN	Misfolded protein material concentrated in cytoplasmic deposits that congregate near the nuclear envelope. `DOI:10.1038/s41556-023-01128-6` Results S1 and S5 and Figures 1 and 4 distinguish cytoplasmic reporter deposits from nuclear INQ and identify a congregation of Q-bodies. `DOI:10.3389/fmolb.2024.1427542` Results 3.1-3.4 follow reporter sequestration and perinuclear positioning under heat stress.
Hsp104-type disaggregase	Protein	acts on	Reviewed label only (reviewed name; no accession asserted)	HSP104	UNKNOWN	Associated disaggregase localized to cytoplasmic JUNQ by correlated microscopy. This association is not a fixed coat or evidence of universal assembly dependence. `DOI:10.1038/s41556-023-01128-6` Results S5 and Figure 4b-c directly localize Hsp104-positive JUNQ outside the nuclear boundary. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P31539/?page_size=200` All 11 integrated matches inspected through next=null; broader family hits are not exact component identities.
proteasome complex	Protein complex	acts on	`GO:0000502`		UNKNOWN	Historically reported proteolytic machinery recruited to JUNQ-designated reporter inclusions, not an invariant constituent or universal formation requirement. Early perinuclear assignments can include nuclear INQ and are not all reclassified as modern cytoplasmic JUNQ. `DOI:10.1038/nature07195` Results S4 and Figure 5d describe 26S proteasome enrichment at JUNQ-designated inclusions, including mutant actin without proteasome inhibition; this is conditional historical association. `DOI:10.1038/s41556-023-01128-6` Results S2 show that proteasome inhibition can cause additional nuclear reporter inclusions, limiting retrospective interpretation of earlier JUNQ assignments. `GO:0000502` Native QuickGO verifies the generic cellular-component class proteasome complex; the label is deliberately not the narrower 26S proteasome identity.

Organism-specific protein examples

Named proteins in which each component's role was established, with the organism the evidence comes from. The component above is the taxon-agnostic family; these are the specific entries behind it.

Hsp104-type disaggregase

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P31539`	Heat shock protein 104	HSP104	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example, not a reassignment of experimental strains to S288C. `UniProtKB:P31539` Native reviewed entry verifies accession, name, gene and reference taxon. `DOI:10.1038/s41556-023-01128-6` Figure 4b-c uses endogenously tagged Hsp104-GFP and correlated cryo-soft X-ray tomography to identify cytoplasmic JUNQ separately from HTT-positive IPOD.

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — Species demonstrated in nuclear-envelope-resolved microscopy and reporter perturbations. Methods defer strain details to an unread supplemental table; individual 2023 assays are not assigned a finer taxon. [DOI:10.1038/s41556-023-01128-6]
NCBITaxon:1247190 Saccharomyces cerevisiae BY4741 — Methods Table 2 identifies BY4741 wild type and derived mutant backgrounds for the 2024 experiments. Native NCBI taxonomy verifies this strain ID; the mutants are derivatives, not assertions that their genotype is wild type. [DOI:10.3389/fmolb.2024.1427542]
NCBITaxon:559292 Saccharomyces cerevisiae S288C — Reference-sequence taxon for the reviewed Hsp104 example only, not a replacement for the experimental BY4741 background. [UniProtKB:P31539]

Functions

spatial sequestration of cytoplasmic misfolded proteins — Concentrates selected misfolded proteins in cytoplasmic deposits near the nucleus. This does not imply that every misfolded protein enters JUNQ or that deposition universally protects cells.
- DOI:10.1038/s41556-023-01128-6 Results S1 and S5, Figures 1 and 4: reporter localization and correlated microscopy resolve cytoplasmic JUNQ.
- DOI:10.3389/fmolb.2024.1427542 Results 3.1-3.4 distinguish perinuclear congregation from peripheral reporter deposition.
conditional clearance of sequestered protein cargo — JUNQ-associated reporter cargo can be cleared through vacuolar and proteasome-associated routes under tested conditions. Their relative contributions depend on reporter and assay; the precise membrane route into the vacuole remains unresolved.
- DOI:10.1038/s41556-023-01128-6 Results S8 and Figure 7 combine cytoplasmic Keima acidification, reporter turnover and protease-sensitive fragments; direct time-resolved budding in Figure 8 concerns INQ, not JUNQ.
- DOI:10.3389/fmolb.2024.1427542 Results 3.5 and Discussion show Atg1/Atg8-sensitive clearance but little bortezomib effect in these NES-LuciTs assays, and leave the route into the vacuole open.
conditional retention of recoverable reporter protein — In the original JUNQ-designated Ubc9Ts assay, cooling restores diffuse fluorescence in an Hsp104-sensitive manner, consistent with a recoverable protein pool. This is not a universal client-refolding claim or a direct activity measurement, and early compartment assignments have nomenclature limitations.
- DOI:10.1038/nature07195 Results S6 and Figure 6e describe fluorescence recovery after temperature downshift and Hsp104/guanidinium perturbation.
- DOI:10.1038/s41556-023-01128-6 Results S2 delimit historical JUNQ assignments in proteasome-inhibited cells by resolving additional nuclear INQ.

Mechanism graphs

Conditional assembly and sorting of cytoplasmic reporter deposits (ASSEMBLY)

Heat-induced misfolding, Q-body congregation and sorting perturbations are distinct experimental readouts.

Subject	Predicate	Object	Evidence
Heat shift to 37 C	induces	Temperature-sensitive misfolded reporter cargo	`DOI:10.1038/s41556-023-01128-6` Results S1 and Figure 1.
Temperature-sensitive misfolded reporter cargo	accumulates in	Cytoplasmic Q-body deposits	`DOI:10.1038/s41556-023-01128-6` Results S5 and Figure 4d-f.
Cytoplasmic Q-body deposits	congregate into	juxtanuclear quality control compartment	`DOI:10.1038/s41556-023-01128-6` Results S5 and Figure 4d describe the cryo-SXT architecture.
Temperature-sensitive misfolded reporter cargo	can accumulate in	Peripheral reporter foci	`DOI:10.3389/fmolb.2024.1427542` Results 3.4 and Figure 4 distinguish reporter locations across sorting mutants.
Combined SSA1 and SSA2 deletion	impairs	juxtanuclear quality control compartment	`DOI:10.3389/fmolb.2024.1427542` Results 3.2 and Figure 2.
BTN2 deletion	impairs	juxtanuclear quality control compartment	`DOI:10.3389/fmolb.2024.1427542` Results 3.4 and Figure 4.
HSP42 deletion	reduces	Peripheral reporter foci	`DOI:10.3389/fmolb.2024.1427542` Results 3.4 and Figure 4; this is not an obligatory Hsp42 requirement for JUNQ formation.

Conditional positioning and INQ/JUNQ convergence (FUNCTION)

Coexpressed inclusions remain separated by the nuclear envelope while converging spatially.

Subject	Predicate	Object	Evidence
juxtanuclear quality control compartment	participates in	Spatial INQ/JUNQ convergence across the nuclear envelope	`DOI:10.1038/s41556-023-01128-6` Results S3 and Figure 3a-c.
CHM7 deletion	impairs	Spatial INQ/JUNQ convergence across the nuclear envelope	`DOI:10.1038/s41556-023-01128-6` Results S7 and Figure 6b.
VPS23 deletion	disrupts	Spatial INQ/JUNQ convergence across the nuclear envelope	`DOI:10.1038/s41556-023-01128-6` Results S7, Figure 6c and described Extended Data Figure 6b; extended-data pixels not inspected.
VPS34 deletion	disrupts	Spatial INQ/JUNQ convergence across the nuclear envelope	`DOI:10.1038/s41556-023-01128-6` Results S7, Figure 6c and described Extended Data Figure 6b.
VPS15 deletion	disrupts	Spatial INQ/JUNQ convergence across the nuclear envelope	`DOI:10.1038/s41556-023-01128-6` Results S7, Figure 6c and described Extended Data Figure 6b.
NUP120 deletion with clustered nuclear pores	biases	JUNQ adjacency to clustered nuclear pores	`DOI:10.1038/s41556-023-01128-6` Results S4 and Figure 3d; this is a positioning observation under intervention, not proof that Nup120 is required for JUNQ formation.

Perturbations of JUNQ-associated cargo clearance (DISASSEMBLY)

Separate reporter assays support conditional vacuolar clearance and persistence phenotypes.

Subject	Predicate	Object	Evidence
juxtanuclear quality control compartment	can undergo	Clearance of JUNQ-associated reporter cargo	`DOI:10.1038/s41556-023-01128-6` Results S8 and Figure 7d,f-g. NES-Keima imaging samples different fields because of photobleaching; the panel-d caption contains an NLS/NES inconsistency.
NVJ1 deletion	impairs	Clearance of JUNQ-associated reporter cargo	`DOI:10.1038/s41556-023-01128-6` Results S6 and Figure 5h, right-hand NES-LuciTs quantification.
VAC8 deletion	impairs	Clearance of JUNQ-associated reporter cargo	`DOI:10.1038/s41556-023-01128-6` Results S6 and Figure 5h, right-hand NES-LuciTs quantification.
VPS4 deletion	impairs	Clearance of JUNQ-associated reporter cargo	`DOI:10.1038/s41556-023-01128-6` Results S7 and Figure 6e quantify NES- as well as NLS-LuciTs puncta.
ATG1 deletion	impairs	Clearance of JUNQ-associated reporter cargo	`DOI:10.3389/fmolb.2024.1427542` Results 3.5 and Figure 5.
ATG8 deletion	impairs	Clearance of JUNQ-associated reporter cargo	`DOI:10.3389/fmolb.2024.1427542` Results 3.5 and Figure 5.
PEP4 deletion with PMSF vacuolar-protease inhibition	impairs	Clearance of JUNQ-associated reporter cargo	`DOI:10.1038/s41556-023-01128-6` Results S8 and Figure 7f-g plus Results description of turnover experiments.

Discussions

INTERPRETATION (RESOLVED): Keep modern cytoplasmic JUNQ separate from INQ, IPOD and related deposits. Shared perinuclear proximity and changing nomenclature do not establish exact identity.
CURATION_TODO (OPEN): Resolve exact source-neutral grounding for variable cargo and Hsp104-type machinery. Variable client material and a narrow disaggregase class cannot be grounded by broader sequence families.
INTERPRETATION (RESOLVED): Separate cargo and directly localized machinery from genetic positioning and clearance factors. Deletion dependence alone is not direct residence, fixed composition or essentiality.
INTERPRETATION (RESOLVED): Preserve assay-dependent proteasome effects and the unresolved route of JUNQ entry into the vacuole. Reporter turnover, puncta counts and precise membrane trafficking are different claims.
INTERPRETATION (RESOLVED): Preserve caption and reporter-label discrepancies without silently resolving them. Source metadata, captions, methods and actual pixels do not always agree.
CURATION_TODO (OPEN): Resolve native client inventories, material state, prevalence and exact strain mapping for older assays. Induced reporter observations do not establish universal dimensions, composition or lineage distribution.

Evidence

DOI:10.1038/s41556-023-01128-6 Sontag et al. (2023), PMID 37081164, PMC12349969.1. Native metadata/JATS verified, not retracted. Read Results S1-S8, Discussion S9, strain-table pointer S35, Data availability S46 and main Figure 3-7 captions. Actual figures, supplemental strain table and raw source data were not inspected. TDM metadata is not a Creative Commons hosting licence.
DOI:10.3389/fmolb.2024.1427542 Rolli et al. (2024), PMID 39234568, PMC11372896.1. Read main Methods including strain Table 2, Results 3.1-3.5, Discussion, Data availability and figure captions; actual Figure 2 inspected. Supplemental materials and raw data were not independently inspected.
DOI:10.1038/nature07195 Kaganovich et al. (2008), PMID 18756251, PMC2746971.1. Native metadata/JATS verified, not retracted. Read Results S3-S6, Discussion S7 and Methods Summary S8. Actual figures and supplements were not inspected in this iteration; historical nomenclature is qualified.
GO:0016234 Native QuickGO verifies active inclusion body as a broader cellular-component parent.
GO:0005737 — cytoplasm Native QuickGO verifies active cytoplasm; modern nuclear-envelope-resolved imaging supports cytoplasmic parthood, not nuclear or vacuolar parthood.

Curation history

2026-10-05T09:13:16Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-05T09:21:09Z codex · EXPANDED_RECORD — Added cytoplasmic JUNQ identity, bounded cargo and machinery classes, three intervention graphs, historical and assay-scope discussions, and an inspected CC BY 4.0 figure.

Source: data/structures/inclusion/juxtanuclear_quality_control_compartment.yaml