Intranuclear Inclusions of Mitochondria in Myopathic Extraocular Muscle

1976 ◽  
Vol 34 ◽  
pp. 70-71
Author(s):  
Jacob Davidowitz ◽  
Bruce R. Pachter ◽  
Goodwin M. Breinin
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Extraocular Muscle ◽  
Nuclear Inclusions ◽  
Intranuclear Inclusions ◽  
Inner Nuclear Membrane

Nuclei often display aberrant inclusions which may be variously unbounded or enclosed within single or double membranes. True intranuclear inclusions are distinguishable from pseudoinclusions which represent planes of section through invaginations of the nuclear envelope, insofar as the latter are characteristically bounded by the outer and inner membranes of the indented perinuclear cisterna. It has been suggested that unbounded apparently true nuclear inclusions might in some cases be derived from pseudoinclusions, the enclosing membranes of which had undergone dissolution subsequent to an engulfment process.2,3 This suggestion was posited in the contexts of intranuclear (a) glycogen accumulations, which might also develop by means of in situ mechanisms and (b) membranous structures, which might also develop from proliferations of the inner nuclear membrane.

Intranuclear membranous inclusions in oocytes of a viviparous teleost (Xiphophorus helleri)

1976 ◽  
Vol 22 (2) ◽  
pp. 325-334
Author(s):  
C. Azevedo
Keyword(s):  
Nuclear Membrane ◽  
Inclusion Bodies ◽  
Intranuclear Inclusions ◽  
Late Prophase ◽  
Xiphophorus Helleri ◽  
Inner Nuclear Membrane ◽  
Prophase I ◽  
Fixed Material ◽  
Metabolic Phenomena

Intranuclear inclusions were observed in oocytes of Xiphophorus helleri during prophase I. In osmium-fixed leptotene nuclei, the inclusions were made up of groups of membrane-limited vesicles or tubules with pale contents, situated near the inner nuclear membrane with which some of them exhibited apparent continuities. In zygotene nuclei, larger vesicles also appeared bounded by two or three membranes and containing tubules apparently invaginated from their walls. In pachytene-dictyate nuclei most vesicular bodies had a wall formed by stratified membranes, or were entirely made up of membranous whorls. In glutaraldehyde-osmium fixed material some of these myeline-like bodies showed a peculiar arrangement, consisting of concentric bands each containing thick inner dense lamellae 2-0-3-0 nm thick and a 5-0 nm outer lamella. It is suggested that these inclusion bodies arise from the inner nuclear membrane of oocytes when cells start to grow intensely during prophase I. The bodies seem to become more complex at late prophase, probably by association of individual vesicles and the occurrence of multiple membrane invaginations, which may be related to active metabolic phenomena taking place at this stage in oocytes.

scholarly journals Unrestrained ESCRT-III drives chromosome fragmentation and micronuclear catastrophe

2019 ◽  
Author(s):  
Marina Vietri ◽  
Sebastian W. Schultz ◽  
Aurélie Bellanger ◽  
Carl M. Jones ◽  
Camilla Raiborg ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Genome Stability ◽  
Membrane Deformation ◽  
Chromosome Fragmentation ◽  
Inner Nuclear Membrane ◽  
Membrane Rupture ◽  
Membrane Fission ◽  
Stable Association ◽  
Inner Nuclear Membrane Protein

AbstractThe ESCRT-III membrane fission machinery1,2 restores nuclear envelope integrity during mitotic exit3,4 and interphase5,6. Whereas primary nuclei resealing takes minutes, micronuclear envelope ruptures appear irreversible and result in catastrophic collapse associated with chromosome fragmentation and rearrangements (chromothripsis), thought to be a major driving force in cancer development7-10. Despite its importance11-13, the mechanistic underpinnings of nuclear envelope sealing in primary nuclei and the defects observed in micronuclei remain largely unknown. Here we show that CHMP7, the nucleator of ESCRT-III filaments at the nuclear envelope3,14, and the inner nuclear membrane protein LEMD215 act as a compartmentalization sensor detecting the loss of nuclear integrity. In cells with intact nuclear envelope, CHMP7 is actively excluded from the nucleus to preclude its binding to LEMD2. Nuclear influx of CHMP7 results in stable association with LEMD2 at the inner nuclear membrane that licenses local polymerization of ESCRT-III. Tight control of nuclear CHMP7 levels is critical, as induction of nuclear CHMP7 mutants is sufficient to induce unrestrained growth of ESCRT-III foci at the nuclear envelope, causing dramatic membrane deformation, local DNA torsional stress, single-stranded DNA formation and fragmentation of the underlying chromosomes. At micronuclei, membrane rupture is not associated with repair despite timely recruitment of ESCRT-III. Instead, micronuclei inherently lack the capacity to restrict accumulation of CHMP7 and LEMD2. This drives unrestrained ESCRT-III recruitment, membrane deformation and DNA defects that strikingly resemble those at primary nuclei upon induction of nuclear CHMP7 mutants. Preventing ESCRT-III recruitment suppresses membrane deformation and DNA damage, without restoring nucleocytoplasmic compartmentalization. We propose that the ESCRT-III nuclear integrity surveillance machinery is a double-edged sword, as its exquisite sensitivity ensures rapid repair at primary nuclei while causing unrestrained polymerization at micronuclei, with catastrophic consequences for genome stability16-18.

Function and assembly of nuclear pore complex proteins

1999 ◽  
Vol 77 (4) ◽  
pp. 321-329 ◽  
Author(s):  
Khaldon Bodoor ◽  
Sarah Shaikh ◽  
Paul Enarson ◽  
Sharmin Chowdhury ◽  
Davide Salina ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Nuclear Envelope ◽  
Nuclear Pore Complex ◽  
Nuclear Membrane ◽  
Current View ◽  
Nuclear Pore ◽  
Dynamic Component ◽  
Inner Nuclear Membrane ◽  
Inner Nuclear Membrane Protein ◽  
Nuclear Membrane Protein

Nuclear pore complexes (NPCs) are extremely elaborate structures that mediate the bidirectional movement of macromolecules between the nucleus and cytoplasm. The current view of NPC organization features a massive symmetrical framework that is embedded in the double membranes of the nuclear envelope. It embraces a central channel of as yet ill-defined structure but which may accommodate particles with diameters up to 26 nm provided that they bear specific import/export signals. Attached to both faces of the central framework are peripheral structures, short cytoplasmic filaments, and a nuclear basket assembly, which interact with molecules transiting the NPC. The mechanisms of assembly and the nature of NPC structural intermediates are still poorly understood. However, mutagenesis and expression studies have revealed discrete sequences within certain NPC proteins that are necessary and sufficient for their appropriate targeting. In addition, some details are emerging from observations on cells undergoing mitosis where the nuclear envelope is disassembled and its components, including NPC subunits, are dispersed throughout the mitotic cytoplasm. At the end of mitosis, all of these components are reutilized to form nuclear envelopes in the two daughter cells. To date, it has been possible to define a time course of postmitotic assembly for a group of NPC components (CAN/Nup214, Nup153, POM121, p62 and Tpr) relative to the integral inner nuclear membrane protein LAP2 and the NPC membrane glycoprotein gp210. Nup153, a dynamic component of the nuclear basket, associates with chromatin towards the end of anaphase coincident with, although independent of, the inner nuclear membrane protein, LAP2. Assembly of the remaining proteins follows that of the nuclear membranes and occurs in the sequence POM121, p62, CAN/Nup214 and gp210/Tpr. Since p62 remains as a complex with three other NPC proteins (p58, p54, p45) during mitosis, and CAN/Nup214 maintains a similar interaction with its partner, Nup84, the relative timing of assembly of these additional four proteins may also be inferred. These observations suggest that there is a sequential association of NPC proteins with chromosomes during nuclear envelope reformation and the recruitment of at least eight of these precedes that of gp210. These findings support a model in which it is POM121 rather than gp210 that defines initial membrane-associated NPC assembly intermediates and which may therefore represent an essential component of the central framework of the NPC. Key words: nuclear pore complex, nucleoporin, mitosis, nuclear transport

scholarly journals SUN-1 and ZYG-12, Mediators of Centrosome–Nucleus Attachment, Are a Functional SUN/KASH Pair in Caenorhabditis elegans

2009 ◽  
Vol 20 (21) ◽  
pp. 4586-4595 ◽  
Author(s):  
IL Minn ◽  
Melissa M. Rolls ◽  
Wendy Hanna-Rose ◽  
Christian J. Malone
Keyword(s):  
Caenorhabditis Elegans ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Coiled Coil ◽  
Physical Interaction ◽  
Type Ii ◽  
Inner Nuclear Membrane ◽  
Sequence Elements ◽  
Inner Nuclear Membrane Protein ◽  
Sun Domain

Klarsicht/ANC-1/Syne/homology (KASH)/Sad-1/UNC-84 (SUN) protein pairs can act as connectors between cytoplasmic organelles and the nucleoskeleton. Caenorhabditis elegans ZYG-12 and SUN-1 are essential for centrosome–nucleus attachment. Although SUN-1 has a canonical SUN domain, ZYG-12 has a divergent KASH domain. Here, we establish that the ZYG-12 mini KASH domain is functional and, in combination with a portion of coiled-coil domain, is sufficient for nuclear envelope localization. ZYG-12 and SUN-1 are hypothesized to be outer and inner nuclear membrane proteins, respectively, and to interact, but neither their topologies nor their physical interaction has been directly investigated. We show that ZYG-12 is a type II outer nuclear membrane (ONM) protein and that SUN-1 is a type II inner nuclear membrane protein. The proteins interact in the luminal space of the nuclear envelope via the ZYG-12 mini KASH domain and a region of SUN-1 that does not include the SUN domain. SUN-1 is hypothesized to restrict ZYG-12 to the ONM, preventing diffusion through the endoplasmic reticulum. We establish that ZYG-12 is indeed immobile at the ONM by using fluorescence recovery after photobleaching and show that SUN-1 is sufficient to localize ZYG-12 in cells. This work supports current models of KASH/SUN pairs and highlights the diversity in sequence elements defining KASH domains.

scholarly journals SINC, a type III secreted protein of Chlamydia psittaci, targets the inner nuclear membrane of infected cells and uninfected neighbors

2015 ◽  
Vol 26 (10) ◽  
pp. 1918-1934 ◽  
Author(s):  
Sergio A. Mojica ◽  
Kelley M. Hovis ◽  
Matthew B. Frieman ◽  
Bao Tran ◽  
Ru-ching Hsia ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Lamina ◽  
Chlamydia Psittaci ◽  
Hek293 Cells ◽  
Secreted Protein ◽  
Inner Nuclear Membrane ◽  
Type Iii ◽  
Infected Cells ◽  
Digitonin Permeabilization

SINC, a new type III secreted protein of the avian and human pathogen Chlamydia psittaci, uniquely targets the nuclear envelope of C. psittaci–infected cells and uninfected neighboring cells. Digitonin-permeabilization studies of SINC-GFP–transfected HeLa cells indicate that SINC targets the inner nuclear membrane. SINC localization at the nuclear envelope was blocked by importazole, confirming SINC import into the nucleus. Candidate partners were identified by proximity to biotin ligase-fused SINC in HEK293 cells and mass spectrometry (BioID). This strategy identified 22 candidates with high confidence, including the nucleoporin ELYS, lamin B1, and four proteins (emerin, MAN1, LAP1, and LBR) of the inner nuclear membrane, suggesting that SINC interacts with host proteins that control nuclear structure, signaling, chromatin organization, and gene silencing. GFP-SINC association with the native LEM-domain protein emerin, a conserved component of nuclear “lamina” structure, or with a complex containing emerin was confirmed by GFP pull down. Our findings identify SINC as a novel bacterial protein that targets the nuclear envelope with the capability of globally altering nuclear envelope functions in the infected host cell and neighboring uninfected cells. These properties may contribute to the aggressive virulence of C. psittaci.

Reticulon-like REEP4 at the inner nuclear membrane promotes nuclear pore complex formation

2021 ◽  
Vol 221 (2) ◽  
Author(s):  
Banafsheh Golchoubian ◽  
Andreas Brunner ◽  
Helena Bragulat-Teixidor ◽  
Annett Neuner ◽  
Busra A. Akarlar ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Pore Complex ◽  
Nuclear Membrane ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Inner Nuclear Membrane ◽  
Pore Complexes ◽  
Late Stages ◽  
Protein Complex Assembly

Nuclear pore complexes (NPCs) are channels within the nuclear envelope that mediate nucleocytoplasmic transport. NPCs form within the closed nuclear envelope during interphase or assemble concomitantly with nuclear envelope reformation in late stages of mitosis. Both interphase and mitotic NPC biogenesis require coordination of protein complex assembly and membrane deformation. During early stages of mitotic NPC assembly, a seed for new NPCs is established on chromatin, yet the factors connecting the NPC seed to the membrane of the forming nuclear envelope are unknown. Here, we report that the reticulon homology domain protein REEP4 not only localizes to high-curvature membrane of the cytoplasmic endoplasmic reticulum but is also recruited to the inner nuclear membrane by the NPC biogenesis factor ELYS. This ELYS-recruited pool of REEP4 promotes NPC assembly and appears to be particularly important for NPC formation during mitosis. These findings suggest a role for REEP4 in coordinating nuclear envelope reformation with mitotic NPC biogenesis.

Sequential PKC- and Cdc2-mediated phosphorylation events elicit zebrafish nuclear envelope disassembly

1999 ◽  
Vol 112 (6) ◽  
pp. 977-987 ◽  
Author(s):  
P. Collas
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Lamina ◽  
Cdc2 Kinase ◽  
Lamin B ◽  
Inner Nuclear Membrane ◽  
Nuclear Envelope Breakdown ◽  
Simultaneous Inhibition ◽  
Integral Proteins

Molecular markers of the zebrafish inner nuclear membrane (NEP55) and nuclear lamina (L68) were identified, partially characterized and used to demonstrate that disassembly of the zebrafish nuclear envelope requires sequential phosphorylation events by first PKC, then Cdc2 kinase. NEP55 and L68 are immunologically and functionally related to human LAP2beta and lamin B, respectively. Exposure of zebrafish nuclei to meiotic cytosol elicits rapid phosphorylation of NEP55 and L68, and disassembly of both proteins. L68 phosphorylation is completely inhibited by simultaneous inhibition of Cdc2 and PKC and only partially blocked by inhibition of either kinase. NEP55 phosphorylation is completely prevented by inhibition or immunodepletion of cytosolic Cdc2. Inhibition of cAMP-dependent kinase, MEK or CaM kinase II does not affect NEP55 or L68 phosphorylation. In vitro, nuclear envelope disassembly requires phosphorylation of NEP55 and L68 by both mammalian PKC and Cdc2. Inhibition of either kinase is sufficient to abolish NE disassembly. Furthermore, novel two-step phosphorylation assays in cytosol and in vitro indicate that PKC-mediated phosphorylation of L68 prior to Cdc2-mediated phosphorylation of L68 and NEP55 is essential to elicit nuclear envelope breakdown. Phosphorylation elicited by Cdc2 prior to PKC prevents nuclear envelope disassembly even though NEP55 is phosphorylated. The results indicate that sequential phosphorylation events elicited by PKC, followed by Cdc2, are required for zebrafish nuclear disassembly. They also argue that phosphorylation of inner nuclear membrane integral proteins is not sufficient to promote nuclear envelope breakdown, and suggest a multiple-level regulation of disassembly of nuclear envelope components during meiosis and at mitosis.

scholarly journals Membrane-anchored growth factor, HB-EGF, on the cell surface targeted to the inner nuclear membrane

2008 ◽  
Vol 180 (4) ◽  
pp. 763-769 ◽  
Author(s):  
Miki Hieda ◽  
Mayumi Isokane ◽  
Michiko Koizumi ◽  
Chiduru Higashi ◽  
Taro Tachibana ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Transmembrane Protein ◽  
Active Form ◽  
Type I ◽  
Transcriptional Repressors ◽  
Sequence Element ◽  
Inner Nuclear Membrane

Heparin-binding EGF-like growth factor (HB-EGF) is synthesized as a type I transmembrane protein (proHB-EGF) and expressed on the cell surface. The ectodomain shedding of proHB-EGF at the extracellular region on the plasma membrane yields a soluble EGF receptor ligand and a transmembrane-cytoplasmic fragment (HB-EGF-CTF). The cytoplasmic domain of proHB-EGF (HB-EGF-cyto) interacts with transcriptional repressors to reverse their repressive activities. However, how HB-EGF-cyto accesses transcriptional repressors is yet unknown. The present study demonstrates that, after exposure to shedding stimuli, both HB-EGF-CTF and unshed proHB-EGF translocate to the nuclear envelope. Immunoelectron microscopy and digitonin-permeabilized cells showed that HB-EGF-cyto signals are at the inner nuclear membrane. A short sequence element within the HB-EGF-cyto allows a transmembrane protein to localize to the nuclear envelope. The dominant-active form of Rab5 and Rab11 suppressed nuclear envelope targeting. Collectively, these data demonstrate that membrane-anchored HB-EGF is targeted to the inner nuclear membrane via a retrograde membrane trafficking pathway.

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