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PubMed1988

Remodeling of mouse thymocyte nuclei depends on the time of their transfer into activated, homologous oocytes.

The potential of parthenogenetically activated mouse oocytes to remodel somatic cell nuclei was studied by ultrastructural means using oocyte-thymocyte hybrids. Complete nuclear remodeling, initiated by nuclear envelope breakdown and chromosome condensation (which is followed by formation of pronucleus-like nucleus) is possible only during a short time gap between metaphase II and telophase of meiotic division. Maturation-promoting factor activity is high during this period. The thymocyte nucleus can follow the sequence of morphological changes only in concert with the development of the native nucleus and only after exposure of the chromatin to the ooplasm. If hybridization is effected with pronucleate oocytes, the thymocyte nucleus retains its interphase character but shows particular modifications in nucleolar morphology (identical to changes observed during reactivation of the nucleolus in stimulated lymphocyte) and in the activity of the nuclear envelope (blebbing). Thus the nucleus not exposed to maturation-promoting factor activity may be influenced by a 'programme' specific for oocyte (blebbing) and by a programme inherent in the introduced somatic cell nucleus.

Animals↗
PubMed1985

Spindle microtubule differentiation and deployment during micronuclear mitosis in Paramecium.

Spindles underwent a 12-fold elongation before anaphase B was completed during the closed mitoses of micronuclei in Paramecium tetraurelia. Two main classes of spindle microtubules have been identified. A peripheral sheath of microtubules with diameters of 27-32 nm was found to be associated with the nuclear envelope and confined to the midportion of each spindle. Most of the other microtubules had diameters of approximately 24 nm and were present along the entire lengths of spindles. Nearly all of the 24-nm microtubules were eliminated from spindle midportions (largely because of microtubule disassembly) at a relatively early stage of spindle elongation. Disassembly of some of these microtubules also occurred at the ends of spindles. About 60% of the total microtubule content of spindles was lost at this stage. Most, perhaps all, peripheral sheath microtubules remained intact. Many of them detached from the nuclear envelope and regrouped to form a compact microtubule bundle in the spindle midportion. There was little, if any, further polymerization of 24-nm microtubules after the disassembly phase. Polymerization of microtubules with diameters of 27-32 nm continued as spindle elongation progressed. Most microtubules in the midportions of well-elongated spindles were constructed from 14-16 protofilaments. A few 24-nm microtubules with 13 protofilaments were also present. The implications of these findings for spatial control of microtubule assembly, disassembly, positioning, and membrane association, that apparently discriminate between microtubules with different protofilament numbers have been explored. The possibility that microtubule sliding occurs during spindle elongation has also been considered.

Animals↗
PubMed1984

A subset of non-histone nuclear proteins reversibly stabilized by the sulfhydryl cross-linking reagent tetrathionate. Polypeptides of the internal nuclear matrix.

When rat liver nuclei are isolated in the presence of the irreversible sulfhydryl-blocking reagent iodoacetamide, digested with DNase I and RNase A, and extracted with 1.6 M NaCl, nuclear envelope (NE) spheres depleted of intranuclear material, as analysed by thin-section electron microscopy, are obtained. Two-dimensional isoelectric focusing (IEF)/SDS-PAGE and non-equilibrium pH gradient electrophoresis (NEPHGE)/SDS-PAGE reveal that the predominant polypeptides are lamins A, B and C. Nuclei isolated in the absence of sulfhydryl blocking reagents yield salt- and nuclease-resistant structures which contain sparse but demonstrable intranuclear material. A number of non-histone polypeptides are seen in addition to the lamins. Nuclei treated with the sulfhydryl cross-linking reagent sodium tetrathionate (NaTT) yield, after exposure to nucleases and 1.6 M NaCl, nuclear matrix-like structures containing an extensive intranuclear network and components of the nucleolus in addition to the NE. Increased amounts of the non-lamin, non-histone polypeptides are recovered with these structures. Subsequent treatment of these NaTT-cross-linked structures with reducing agents in 1.0 M NaCl selectively solubilizes the intranuclear components but leaves the nuclear envelope apparently intact. The lamins remain sedimentable and are virtually absent from the soluble (intranuclear) material. Instead, the major solubilized polypeptides are (a) 68 and 63 kD polypeptides which migrate in the vicinity of lamins B and C, respectively, but are distinguishable from the lamins by immunoblotting and by uni-dimensional peptide mapping; (b) a series of basic 60-70 kD polypeptides (pI greater than 8.0) which are not recognized by anti-lamin antisera; (c) an acidic (pI 5.3) 38 kD polypeptide; and (d) a number of high molecular mass (greater than 100 kD) polypeptides. These observations not only suggest a convenient method for fractionating matrix structures from rat liver nuclei into biochemically and morphologically discrete components, but also identify a subset of major non-lamin, non-histone nuclear polypeptides (comprising approx. 20% of the total nuclear protein) whose intermolecular interactions can be reversibly stabilized apparently by intermolecular disulfide bond formation by NaTT.

Animals↗
PubMed1989

Energy requirement and kinetics of transport of poly(A)-free histone mRNA compared to poly(A)-rich mRNA from isolated L-cell nuclei.

ATP-promoted efflux of poly(A)-rich RNA from isolated nuclei of prelabeled mouse lymphoma L5178y cells has an activation energy of 51.5 kJ/mol, similar to that found for the nuclear envelope nucleoside triphosphatase (48.1 kJ/mol) assumed to be involved in mediating nucleocytoplasmic transport of at least some RNA. Here we show that efflux of two specific poly(A)-rich mRNAs (actin and beta-tubulin) from isolated L-cell nuclei is almost totally dependent on the presence of ATP, while efflux of poly(A)-free histone mRNA (H4, H2B, and H1) also occurs to a marked extent in the absence of this nucleotide. Measurements of temperature dependence of transport rate revealed an activation energy of 56.1 kJ/mol for actin mRNA, while the activation energy for histone-H4-mRNA efflux was in the same range as that found for ATP-induced release of RNA from demembranated nuclei (about 15-20 kJ/mol). Addition of nonhydrolyzable nucleotide analogs of ATP to the in vitro system used for measurement of RNA transport did not result in release of nonhistone mRNA (actin), but enhanced the efflux of H4 mRNA to approximately the same extent as ATP. Although not absolutely required, addition of ATP stimulated the rate of export of histone mRNA about twofold. Only the poly(A)-rich RNA, but not the poly(A)-free RNA, released from isolated nuclei was found to compete with poly(A) for the nuclear envelope mRNA-binding site, indicating the mechanism of transport for both RNA classes to be distinct. Export of both nonhistone and histone mRNA was found to be inhibited by a monoclonal antibody against a p60 nuclear-pore-complex antigen. This antibody had no effect on the nucleoside triphosphatase, mediating transport of poly(A)-rich mRNA.

Animals↗
PubMed1996

Nuclear and cellular size of myocytes in different segments of the developing rat heart.

BACKGROUND: In the embryonic heart, the individual cardiac segments show different growth rates. For the analysis of changing form in relation with changing function, data on number and shape of cardiomyocytes are necessary. Such data will give insight into the process of hypertrophy and/or hyperplasia as they may take place in the myocardium in the embryonic period. METHODS: We have measured the volumes of the nuclei and myocytes as well as the surface areas of the nuclear envelope and cellular membrane using stereological tools in rat embryos from 11 days postcoitum to 17 days postcoitum. From the data of the cellular volume of the myocytes and the myocardial volume of the individual segments, we have calculated the total number of myocytes during the developmental period. RESULTS: It is shown that the sinus venosus, sinu-atrial junction, and atrium increase their cellular volume during development, whereas the other cardiac segments show no difference in cellular volume. Similarly, the surface area of the cell membrane of the sinus venosus and sinu-atrial junction had increased during development. The nuclear volume and the surface area of the nuclear envelope did not differ during the period studied. The total number of myocytes showed a conspicuously smaller increase in the atrio-ventricular canal and distal outlet segment than in the other segments. CONCLUSIONS: The increase of the cellular volume in the segments sinus venosus and sinu-atrial junction seems to be due to a late differentiation process. In general, however, the increase of the myocardial volume in the individual cardiac segments is caused by hyperplasia of the cardiomyocytes in these segments and not by hypertrophy. The surface area of cells has a fixed relationship with cell volume, indicating that no important changes take place in the developmental period studied.

Age Factors↗
PubMed1983

A difference in the nucleoli of Purkinje cells of the nodular lobe of the hamster cerebellum.

Purkinje cells of the hamster cerebellum typically contain a large, single, centrally located nucleolus. Strikingly different are Purkinje cells concentrated in the nodular cortex, which characteristically contain several small, pale-staining nucleoli, most of which are peripherally located, in contact with the nuclear envelope. These atypical cells are also smaller, their Nissl bodies stain less intensely, and their nuclear envelopes appear more invaginated. Functional differences are implicit.

Animals↗
PubMed2005

Spindle assembly: asters part their separate ways.

Cells have developed diverse ways to separate two microtubule asters to form a mitotic spindle. Here, I focus on two mechanisms used to position asters around chromosomes during mitosis: first, aster migration around the nuclear envelope and, second, aster attachment to a contractile cortex at the plasma membrane after the nuclear envelope has broken down. Although certain cell types use one mechanism predominantly, most rely on both to ensure proper spindle assembly.

Animals↗
PubMed1989

Distribution of protein disulfide isomerase in rat epiphyseal chondrocytes.

We investigated the intracellular distribution of protein disulfide isomerase (PDI) in rat epiphyseal chondrocytes by immunocytochemistry, using a post-embedding protein A-gold technique. Gold particles were localized primarily in the cisternal space of the rough endoplasmic reticulum (ER) and nuclear envelopes. The ER cisternae of the chondrocytes in all the differentiating epiphyseal zones--resting, proliferative, pre-hypertrophic, and hypertrophic--were equally and highly labeled. The labeling density of the cisternal space of the dilated ER, probably reflecting marked accumulation of secretory proteins such as procollagen, was always higher than that of the non-dilated ER. In the dilated cisternal space, gold particles were freely and evenly distributed, without preferential binding to the luminal surface of the ER membranes. We suggest that PDI catalyzes the formation of disulfide bonds of various secretory proteins, perhaps type II procollagen, in the cisternal space of the ER in epiphyseal chondrocytes. The exclusive localization of gold particles in the cisternal space of the ER and nuclear envelopes and the lack of gold particles in the Golgi apparatus, including cis-Golgi cisternae, indicate that PDI is an ER-soluble protein in the chondrocytes and is presumably sorted out in some pre-Golgi compartment and not transported to the Golgi apparatus.

Aging↗
PubMed2006

Nuclear titin interacts with A- and B-type lamins in vitro and in vivo.

Lamins form structural filaments in the nucleus. Mutations in A-type lamins cause muscular dystrophy, cardiomyopathy and other diseases, including progeroid syndromes. To identify new binding partners for lamin A, we carried out a two-hybrid screen with a human skeletal-muscle cDNA library, using the Ig-fold domain of lamin A as bait. The C-terminal region of titin was recovered twice. Previous investigators showed that nuclear isoforms of titin are essential for chromosome condensation during mitosis. Our titin fragment, which includes two regions unique to titin (M-is6 and M-is7), bound directly to both A- and B-type lamins in vitro. Titin binding to disease-causing lamin A mutants R527P and R482Q was reduced 50%. Studies in living cells suggested lamin-titin interactions were physiologically relevant. In Caenorhabditis elegans embryos, two independent C. elegans (Ce)-titin antibodies colocalized with Ce-lamin at the nuclear envelope. In lamin-downregulated [lmn-1(RNAi)] embryos, Ce-titin was undetectable at the nuclear envelope suggesting its localization or stability requires Ce-lamin. In human cells (HeLa), antibodies against the titin-specific domain M-is6 gave both diffuse and punctate intranuclear staining by indirect immunofluorescence, and recognized at least three bands larger than 1 MDa in immunoblots of isolated HeLa nuclei. In HeLa cells that transiently overexpressed a lamin-binding fragment of titin, nuclei became grossly misshapen and herniated at sites lacking lamin B. We conclude that the C-terminus of nuclear titin binds lamins in vivo and might contribute to nuclear organization during interphase.

Amino Acid Sequence↗
PubMed2001

Subdomain-specific localization of CLIMP-63 (p63) in the endoplasmic reticulum is mediated by its luminal alpha-helical segment.

The microtubule-binding integral 63 kD cytoskeleton-linking membrane protein (CLIMP-63; former name, p63) of the rough endoplasmic reticulum (ER) is excluded from the nuclear envelope. We studied the mechanism underlying this ER subdomain-specific localization by mutagenesis and structural analysis. Deleting the luminal but not cytosolic segment of CLIMP-63 abrogated subdomain-specific localization, as visualized by confocal microscopy in living cells and by immunoelectron microscopy using ultrathin cryosections. Photobleaching/recovery analysis revealed that the luminal segment determines restricted diffusion and immobility of the protein. The recombinant full-length luminal segment of CLIMP-63 formed alpha-helical 91-nm long rod-like structures as evident by circular dichroism spectroscopy and electron microscopy. In the analytical ultracentrifuge, the luminal segment sedimented at 25.7 S, indicating large complexes. The complexes most likely arose by electrostatic interactions of individual highly charged coiled coils. The findings indicate that the luminal segment of CLIMP-63 is necessary and sufficient for oligomerization into alpha-helical complexes that prevent nuclear envelope localization. Concentration of CLIMP-63 into patches may enhance microtubule binding on the cytosolic side and contribute to ER morphology by the formation of a protein scaffold in the lumen of the ER.

Animals↗
PubMed1999

Perforin-dependent nuclear targeting of granzymes: A central role in the nuclear events of granule-exocytosis-mediated apoptosis?

Programmed cell death, apoptosis, involves very distinctive changes within the target cell nucleus, including margination of the chromatin, DNA fragmentation and breakdown of the nuclear envelope. Cytolytic granule-mediated target cell apoptosis is effected, in part, through synergistic action of the membrane-acting protein perforin and serine proteases, such as granzymes A or B. Recent work using confocal laser scanning microscopy as well as other techniques supports the idea that perforin-dependent translocation of granzymes to the nucleus of target cells plays a central role in effecting the nuclear changes associated with apoptosis. In vitro experiments indicate that granzyme nuclear import follows a novel pathway, being independent of ATP, not inhibitable by non-hydrolysable GTP analogues and involving binding within the nucleus, unlike conventional signal- dependent nuclear protein import. In intact cells, perforin-dependent nuclear entry of granzymes precedes the nuclear events of apoptosis such as DNA fragmentation and nuclear envelope breakdown; prevention of granzyme nuclear translocation through bcl2 overexpression or treatment of target cells with inhibitors of caspase activation blocks these events. Nuclear localization of granzymes thus appears to be central to induction of the nuclear changes associated with cytolytic granule-mediated apoptosis.

Animals↗
PubMed2004

Structure-function relationship of biological gels revealed by multiple-particle tracking and differential interference contrast microscopy: the case of human lamin networks.

Lamin B1 filaments organize into a thin dense meshwork underlying the nucleoplasmic side of the nuclear envelope. Recent experiments in vivo suggest that lamin B1 plays a key structural role in the nuclear envelope, but the intrinsic mechanical properties of lamin B1 networks remain unknown. To assess the potential mechanical contribution of lamin B1 in maintaining the integrity and providing structural support to the nucleus, we measured the micromechanical properties and examined the ultrastructural distribution of lamin B1 networks in vitro using particle tracking methods and differential interference contrast (DIC) microscopy. We exploit various surface chemistries of the probe microspheres (carboxylated, polyethylene glycol-coated, and amine-modified) to differentiate lamin-rich from lamin-poor regions and to rigorously extract local viscoelastic moduli from the mean-squared displacements of noninteracting particles. Our results show that human lamin B1 can, even in the absence of auxiliary proteins, form stiff and yet extremely porous networks that are well suited to provide structural strength to the nuclear lamina. Combining DIC microscopy and particle tracking allows us to relate directly the local organization of a material to its local mechanical properties, a general methodology that can be extended to living cells.

Diffusion↗
PubMed1993

Retrograde lipid traffic in yeast: identification of two distinct pathways for internalization of fluorescent-labeled phosphatidylcholine from the plasma membrane.

Digital, video-enhanced fluorescence microscopy and spectrofluorometry were used to follow the internalization into the yeast Saccharomyces cerevisiae of phosphatidylcholine molecules labeled on one acyl chain with the fluorescent probe 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD). Two pathways were found: (1) transport by endocytosis to the vacuole and (2) transport by a non-endocytic pathway to the nuclear envelope and mitochondria. The endocytic pathway was inhibited at low temperature (< 2 degrees C) and by ATP depletion. Mutations in secretory (SEC) genes that are necessary for membrane traffic through the secretory pathway (including SEC1, SEC2, SEC4, SEC6, SEC7, SEC12, SEC14, SEC17, SEC18, and SEC21) almost completely blocked endocytic uptake. In contrast, mutations in the SEC63, SEC65, or SEC11 genes, required for translocation of nascent secretory polypeptides into the ER or signal peptide processing in the ER, only slightly reduced endocytic uptake. Phospholipid endocytosis was also independent of the gene encoding the clathrin heavy chain, CHC1. The correlation of biochemical analysis with fluorescence microscopy indicated that the fluorescent phosphatidylcholine was degraded in the vacuole and that degradation was, at least in part, dependent on the vacuolar proteolytic cascade. The non-endocytic route functioned with a lower cellular energy charge (ATP levels 80% reduced) and was largely independent of the SEC genes. Non-endocytic transport of NBD-phosphatidylcholine to the nuclear envelope and mitochondria was inhibited by pretreatment of cells with the sulfhydryl reagents N-ethylmaleimide and p-chloromercuribenzenesulfonic acid, suggesting the existence of protein-mediated transmembrane transfer (flip-flop) of phosphatidylcholine across the yeast plasma membrane. These data establish a link between lipid movement during secretion and endocytosis in yeast and suggest that phospholipids may also gain access to intracellular organelles through non-endocytic, protein-mediated events.

Adenosine Triphosphate↗
PubMed2003

The desynaptic (dy) and desynaptic1 (dsy1) mutations in maize (Zea mays L) cause distinct telomere-misplacement phenotypes during meiotic prophase.

During meiotic prophase, telomeres actively attach themselves to the nuclear envelope and cluster in an arrangement called the bouquet. The bouquet is unique to meiosis, highly conserved, and thought to facilitate homologous chromosome synapsis. Analy sis of three-dimensional fluorescence in situ hybridization (3-D FISH) image data has been employed to characterize the bouquet in fixed pollen mother cells of maize (Zea mays L.). In order to examine the function of the bouquet further, several meiotic mutants were screened for telomeric defects using 3-D FISH as an assay. Two mutants, desynaptic (dy) and desynaptic1 (dsy1), were found to exhibit novel telomere-misplacement phenotypes. In both cases, the telomere-associated mutant phenotypes occurred prior to what was previously reported as the earliest affected stage. Three alleles of the desynaptic1 mutation (dsy1-1, dsy1-9101, and dsy1-9307) resulted in a partial bouquet phenotype at the zygotene stage of meiotic prophase. By contrast, dy nuclei contained apparently normal bouquets, but then resulted in a premature intranuclear localization of telomeres at the pachytene stage, when telomeres normally disperse but remain attached to the nuclear envelope. The dsy1 mutation is known to impair the fidelity and progression of homologous synapsis, whereas the dy mutation is known to reduce recombination rates. If the telomere misplacements are primary defects of these mutants, then these data would be consistent with the hypothesis that meiotic telomeres have at least two separable functions, one involving proper homologous chromosome synapsis at the bouquet stage and another involving post-bouquet cross-over control.

Fertility↗
PubMed1994

Cell cycle dependent distribution of a centrosomal antigen at the perinuclear MTOC or at the kinetochores of higher plant cells.

Compelling evidence has been obtained in favour of the idea that the nuclear surface of higher plant cells is a microtubule-nucleating and/or organizing site (MTOC), in the absence of defined centrosomes. How these plant MTOC proteins are redistributed and function during the progression of the cell cycle remains entirely unknown. Using a monoclonal antibody (mAb 6C6) raised against isolated calf thymus centrosomes and showing apparent reaction with the plant nuclear surface, we followed the targeted antigen distribution during mitosis and meiosis of higher plants. Immunoblot analysis of protein fractions from Allium root meristematic cell extracts probed with mAb 6C6 reveals a polypeptide of an apparent Mr of 78000. In calf centrosome extracts, a polypeptide of comparable molecular mass is found in addition to a major antigen of Mr 180000 after mAb 6C6 immunoblotting. During mitotic initiation, the plant antigen is prominent on the periphery of the prophase nucleus. When the nuclear envelope breaks down, the antigen suddenly becomes associated with the centromere-kinetochores until late anaphase. In telophase, when the nuclear envelope is being reconstructed, it is no longer detected at the kinetochores but is solely associated again with the nuclear surface. This antigen displays a unique spatial and temporal distribution, which may reflect the pathway of plant protein(s) between the nuclear surface and the kinetochores under cell cycle control. So far, such processes have not been described in higher plant cells. These observations shed light on the putative activity of the plant kinetochore as a protein transporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Allium↗
PubMed1998

Dynein and dynactin are localized to astral microtubules and at cortical sites in mitotic epithelial cells.

The mitotic spindle is often positioned in a characteristic location during development, for example to enable the proper segregation of developmental determinants [1,2]. When epithelial cells divide, the mitotic spindle is often positioned parallel to the plane of the epithelium, so that both daughter cells contribute to the epithelium [3]. The mechanisms by which mitotic spindles are positioned have not been characterized in great detail, but evidence is accumulating that in some systems the dynein-dynactin microtubule motor complex plays a role [4-6]. Dynein has yet not been localized to cortical sites where it could bind to microtubules and exert a force that might orient the mitotic spindle, however [7,8]. Here, we report that in mitotic polarized epithelial cells, the dynein-dynactin complex accumulates, from prometaphase onwards, along astral microtubules and at cortical spots, into which many of the astral microtubules dock. The spots are assembled at the lateral plasma membrane, in the region below the tight junctions. Their formation is inhibited by cytochalasin D, and under these conditions the spindles do not orient properly. This novel localization of the dynein-dynactin complex is consistent with a role for the complex in the positioning of the mitotic spindle. We also show that, during prophase, the motor complex colocalizes with the nuclear envelope, consistent with it having a role in separating the centrosomes that are associated with the nuclear envelope.

Animals↗
PubMed2003

Extraction and analysis of human nuclear and mitochondrial DNA from electron beam irradiated envelopes.

The United States Postal Service is considering methods such as electron beam irradiation to neutralize biological agents sent through the mail. While this is proven to reduce/eliminate pathogenic organisms, it may also degrade human genomic DNA and therefore hinder the ability to garner forensically informative genetic profiles. To determine the effects of electron beam irradiation on DNA typing, 16 white, standard letter-sized envelopes were licked. Half of the envelopes served as nonirradiated controls while the other half underwent irradiation at dosages sufficient to kill anthrax spores (29.3 and 51.6 kGy). Total cellular DNA was extracted from all envelopes; nuclear short tandem repeat loci, as well as the hypervariable region I from mitochondrial DNA, were amplified by means of the polymerase chain reaction. Short tandem repeat profiles and mitochondrial DNA sequence haplotypes were acquired on an ABI Prism 310 Genetic Analyzer platform. Analysis of data from irradiated samples revealed evidence of DNA degradation; however, the ability to construct full genetic profiles from both nuclear and mitochondrial DNA remained largely unaffected. The use of the polymerase chain reaction, coupled with florescent fragment analysis and mitochondrial DNA sequencing, should be considered to profile biological material from evidence enduring irradiation to inactivate infectious agents.

Complementarity Determining Regions↗
PubMed1997

Dynamics of proteasome distribution in living cells.

Proteasomes are proteolytic complexes involved in non-lysosomal degradation which are localized in both the cytoplasm and the nucleus. The dynamics of proteasomes in living cells is unclear, as is their targeting to proteins destined for degradation. To investigate the intracellular distribution and mobility of proteasomes in vivo, we generated a fusion protein of the proteasome subunit LMP2 and the green fluorescent protein (GFP). The LMP2-GFP chimera was quantitatively incorporated into catalytically active proteasomes. The GFP-tagged proteasomes were located within both the cytoplasm and the nucleus. Within these two compartments, proteasomes diffused rapidly, and bleaching experiments demonstrated that proteasomes were transported slowly and unidirectionally from the cytoplasm into the nucleus. During mitosis, when the nuclear envelope has disintegrated, proteasomes diffused rapidly throughout the dividing cell without encountering a selective barrier. Immediately after cell division, the restored nuclear envelope formed a new barrier for the diffusing proteasomes. Thus, proteasomes can be transported unidirectionally over the nuclear membrane, but can also enter the nucleus upon reassembly during cell division. Since proteasomes diffuse rapidly in the cytoplasm and nucleus, they may perform quality control by continuous collision with intracellular proteins, and degrading those proteins that are properly tagged or misfolded.

Antigen Presentation↗