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PubMed1994

Effect of nuclear localization signal-receptor interaction on nuclear envelope-associated ATPase activity.

The possibility that interaction of the nuclear localization signal (NLS) with its pore receptor may directly stimulate nuclear envelope-associated ATPase activity and consequently provide energy for protein translocation across the pore has been studied. ATPase activity was assayed after cross-linking of the prototype NLS peptide with its pore receptor, or after preincubation of envelopes with NLS-albumin conjugates. Neither treatment enhanced enzyme activity. A more complex series of events may be required for energy-generation at the nuclear pore.

Adenosine Triphosphatases↗

PubMed1997

Nuclear translocation of gold labeled-testosterone-bovine serum albumin conjugate through the nuclear double membranes in rat spermatids.

We have demonstrated that testosterone-bovine serum albumin conjugate labeled with 2-nm colloidal gold (testosterone-BSA-gold) injected into the vascular system of rat becomes visible as silver deposits on the sections of tissues embedded in epoxy resin after silver enhancement and enters the androgen-target cell nuclei, e.g. round spermatids, but not the non-target cell nuclei. The diameter of the silver deposits depends on the duration of silver enhancement. In this study, to make clear the transfer route of testosterone-BSA-gold into the round spermatid nucleus, the testis of rat injected testosterone-BSA-gold was observed under electron microscope after silver enhancement for short periods of time. The small silver deposits were present on the cell membrane, vesicles, Golgi region, acrosome, subacrosomal space, both the post-acrosomal and the subacrosomal nuclear envelope, and the nucleoplasm in the cap-phase spermatids. The silver deposits were also found in the perinuclear cisterna of post-acrosomal nuclear envelope, but not in the nuclear pore. When the spermatids were observed at high-power magnification without the silver enhancement, the outer nuclear membrane showed many irregular invaginations toward the inner nuclear membrane in the post-acrosomal nuclear envelope. Furthermore, a double-membrane-like vesicle seemed to be present in the nuclear envelope. In the vesicle, the gold particles were present along the inner membrane. These results suggest that testosterone-BSA-gold can enter the nucleoplasm through some route provided by the nuclear double membranes in both the post-acrosomal and the subacrosomal nuclear envelope.

Acrosome↗

PubMed2005

Nuclear envelopathies--raising the nuclear veil.

The nuclear envelope separates the chromosomes from cytoplasm in eukaryotic cells and consists of three main domains: inner and outer nuclear membranes and nuclear pore complexes. The inner nuclear membrane maintains close associations with the underlying chromatin and nuclear lamina. For many years, the nuclear envelope was thought to function mainly as an architectural stabilizer of the nucleus, participating in assembly and disassembly processes during mitosis. However, recent findings demonstrate that nuclear envelope proteins are involved in fundamental nuclear functions, such as gene transcription and DNA replication, and that inherited or de novo mutated proteins cause human diseases, termed "nuclear envelopathies." These findings emphasize the importance of understanding the functions of this cellular domain, in both physiologic and pathologic states. To date, mutations in the genes encoding the nuclear envelope proteins emerin, MAN1, lamin A/C, and lamin B receptor were found to cause nuclear envelopathies. The diseases that are caused by mutations in LMNA gene are collectively called "laminopathies." Nuclear envelopathies have diverse clinical phenotypes, ranging from cardiac and skeletal myopathies to partial lipodystrophy, peripheral neuropathy, and premature aging. This raises the question of how do such ubiquitously expressed proteins give rise to tissue-specific disease phenotypes. One possible explanation is the involvement of nuclear envelope proteins in the regulation of gene transcription, a novel mechanism that has been the focus of research in our lab in recent years. In this review, we describe recent discoveries in the field of nuclear envelopathies and discuss current proposed pathophysiological mechanisms underlying these diseases.

Animals↗

PubMed1984

Events associated with the initiation of mitosis in fused multinucleate HeLa cells.

Large multinucleate (LMN) HeLa cells with more than 10-50 nuclei were produced by random fusion with polyethylene glycol. The number of nuclei in a particular stage of the cell cycle at the time of fusion was proportionate to the duration of the phase relative to the total cell cycle. The fused cells did not gain generation time. Interaction of various nuclei in these cells has been observed. The nuclei initially belonging to the G1- or S-phase required a much longer time to complete DNA synthesis than in mononucleate cells. Some of the cells reached mitosis 15 h after fusion, whereas others required 24 h. The cells dividing early, contained a larger number of initially early G1-phase nuclei than those cells dividing late. The former very often showed prematurely condensed chromosome (PCC) groups. In cells with a large number of advanced nuclei the few less advanced nuclei could enter mitosis prematurely. On the other hand, the cells having a large number of nuclei belonging initially to late S- or G2-phase took longer to reach mitosis. These nuclei have been taken out of the normal sequence and therefore failed to synthesize the mitotic factors and depended on others to supply them. Therefore the cells as a whole required a longer period to enter mitosis. Although the nuclei became synchronized at metaphase, the cells revealed a gradation in prophase progression in the different nuclei. At the ultrastructural level the effect of advanced nuclei on the less advanced ones was evident with respect to chromosome condensation and nuclear envelope breakdown. Less advanced nuclei trapped among advanced nuclei showed PCC and nuclear envelope breakdown prematurely, whereas mitotic nuclei near interphase or early prophase nuclei retained their nuclear envelopes for a much longer time. PCC is closely related to premature breakdown of the nuclear envelope. Our observations clearly indicate that chromosome condensation and nuclear envelope breakdown are two distinct events. Kinetochores with attached microtubules could be observed on prematurely condensed chromosomes. Kinetochores of fully condensed chromosomes often failed to become connected to spindle elements. This indicates that the formation of a functional spindle is distinct from the other events and may depend on different factors.

Cell Division↗

PubMed1978

Ultrastructure of mitosis in the chloromonadophycean alga Vacuolaria virescens.

During preprophase in the chloromonadophycean alga Vacuolaria virescens microtubules are present around the flagellar basal bodies and extend over the anterior surface of the nucleus. These microtubules assist in the separation of the flagella and later enter the nucleus through polar gaps. During prophase the nucleoli begin to disperse and the chromosomes become condensed. At metaphase the nucleus assumes an elliptical shape and an equatorial plate of chromosomes becomes aligned across the long axis of the nucleus; kinetochores are recognizable on some of the chromosomes. The nuclear envelope remains intact over most of the surface and in places it forms folds. During anaphase chromosomes are less distinct and vesicles are present in the elongating nucleus. Most of the new nuclear envelope around the progeny nuclei is formed by coalescence of these membrane vesicles during late anaphase and telophase, although some of the original nuclear envelope may also become incorporated. During telophase disintegration of the original nuclear envelope becomes pronounced and portions of this structure are recognizable in the cytoplasm after completion of mitosis. It is suggested that this unusual type of nuclear envelope behaviour may be important in ensuring the segregation of the Golgi apparatus and contractile vacuole to progeny cells. Interphase cells contain a single extensive Golgi apparatus which is located between the anterior surface of the nucleus and the contractile vacuole. The Golgi apparatus and contractile vacuole act as an osmoregulatory system and their presence is presumably essential to the existence of the organism. Formation of a new contractile vacuole and division of the Golgi apparatus occur early in mitosis and thereafter a Golgi apparatus and contractile vacuole become associated with each of the poles of the nucleus. They retain this location throughout mitosis and during cytokinesis, with the result that an osmoregulatory system is present in each of the daughter cells. In a similar manner, microbody-like organelles are associated with the nuclear envelope during mitosis but not at interphase. Growth of the nuclear envelope during mitosis may serve as the means of partitioning these organelles to the progeny cells. Thus mitosis in Vacuolaria virescens is responsible not only for the equal segregation of the genetic material but also for the correct distribution of some of the cytoplasmic components.

Cell Nucleus↗

PubMed1983

Immunofluorescence microscopy of tubulin and microtubule arrays in plant cells. I. Preprophase band development and concomitant appearance of nuclear envelope-associated tubulin.

The development of the preprophase band (PPB) of microtubules (MT) in meristematic plant cells was studied by using antibodies to pig brain tubulin and indirect immunofluorescence microscopy. The PPB is first visible as a wide band of MT that are arranged only slightly more densely than flanking MT of the cortical interphase array. MT progressively become more tightly packed together, and other cortical MT are no longer seen as the PPB matures. The surface of the nuclear envelope (NE) displays no tubulin fluorescence during interphase but begins to fluoresce in the early stages of PPB development, and its intensity progressively increases thereafter. The pattern at the NE is usually diffuse at first, suggesting the presence of nonpolymerized tubulin, but fibers along the NE can be resolved at later stages. MT, arranged either radially or as a meshwork, can occur between the nucleus and cell cortex, and sometimes appear to connect the PPB and NE directly. Isolated preprophase nuclei from cells ruptured during processing often retain the PPB in its normal orientation, indicating stable linkages between the nucleus and PPB. Fluorescent cross-bars perpendicular to the axis of the MT were resolved in some PPB, suggesting lateral linkages. This suggestion is reinforced by the presence of PPB that hold together as a ribbon of MT in certain preparations, allowing PPB to be isolated from the rest of the cytoplasm and the nucleus.

Cell Fractionation↗

PubMed2004

Nuclear side conformational changes in the nuclear pore complex following calcium release from the nuclear membrane.

Changes in nuclear pore complex (NPC) structure are studied following treatments modifying the cisternal calcium levels located between the two lipid bilayers that together form the nuclear envelope. Since the NPC forms the only known passageway across the nuclear envelope, it plays a central role in nucleocytoplasmic transport. Understanding the origin of conformational changes that may affect this trafficking or modify cargo interactions with the NPC is, therefore, necessary to completely understand the function of these complex molecules. In previous studies on the cytoplasmic side of the nuclear envelope, a central mass was observed in the pore of the NPC and its location was shown to be sensitive to the cisternal calcium levels. Here we report atomic force microscopy (AFM) measurements on the nuclear side of the envelope, which also reveal a cisternal calcium dependence in the conformational state of the NPC. These measurements, made at the single nuclear pore level, reveal a displacement of the central mass towards the nuclear side of the membrane following treatments with adenophostin A, a specific agonist of calcium channels (inositol 1,4,5-trisphosphate (IP(3)) receptors) located in the nuclear envelope. We further demonstrate that these conformational changes are observed in nuclear pores lacking the basket structure while samples prepared in the presence of protease inhibitors retain baskets and block AFM measurements of the channel. While these measurements are unable to distinguish whether the central mass is cargo or an integral component of the NPC, its dose-dependent displacement with cisternal calcium levels does suggest links to transport or to changes in cargo interactions with the NPC. Taken together with previous measurements done on the cytoplasmic side of the nuclear envelope, these studies argue against a piston-like displacement of the central mass and instead suggest a more complicated mechanism. One possibility involves a concerted collapse of the NPC rings towards one another following cisternal calcium release, thus leading to the apparent emergence of the central mass from each side of the NPC.

Active Transport, Cell Nucleus↗

PubMed2006

Spatially regulated ubiquitin ligation by an ER/nuclear membrane ligase.

The ubiquitin system targets many cellular proteins. Doa10 (also known as Ssm4), a yeast transmembrane ubiquitin ligase (E3), resides in the endoplasmic reticulum (ER), but it attaches ubiquitin to soluble proteins that concentrate in the nucleus. A central question is how nuclear substrates gain access to an enzyme in the ER. Here we show that Doa10 reaches the inner nuclear membrane. A subcomplex of nuclear pore subunits is important for this transport. Notably, another ER transmembrane E3, Hrd1 (also known as Der3), cannot localize efficiently to the inner nuclear membrane. Tethering Doa10 at the cell periphery inhibits degradation of soluble nuclear substrates but not cytoplasmic ones. If Doa10 is released from these peripheral sites, localization of Doa10 to the nuclear envelope and degradation of its nuclear substrates are restored in parallel. Thus, localization of Doa10 to the inner nuclear membrane is necessary for nuclear substrate degradation. These data indicate that different membrane ubiquitin ligases are spatially sorted within the ER-nuclear envelope membrane system and that this differential localization contributes to their specificity.

Endoplasmic Reticulum↗

PubMed2005

Intact actin filaments are required for cytosolic phospholipase A2 translocation but not for its activation by norepinephrine in vascular smooth muscle cells.

Cytosolic phospholipase A(2) (cPLA(2)) is activated and translocated to the nuclear envelope by various vasoactive agents, including norepinephrine (NE), and releases arachidonic acid (AA) from tissue phospholipids. We previously demonstrated that NE-induced cPLA(2) translocation to the nuclear envelope is mediated via its phosphorylation by calcium/calmodulin-dependent kinase-II in rabbit vascular smooth muscle cells (VSMCs). Cytoskeletal structures actin and microtubule filaments have been implicated in the trafficking of proteins to various cellular sites. This study was conducted to investigate the contribution of actin and microtubule filaments to cPLA(2) translocation to the nuclear envelope and its activation by NE in rabbit VSMCs. NE (10 microM) caused cPLA(2) translocation to the nuclear envelope as determined by immunofluorescence. Cytochalasin D (CD; 0.5 microM) and latrunculin A (LA; 0.5 microM) that disrupted actin filaments, blocked cPLA(2) translocation elicited by NE. On the other hand, disruption of microtubule filaments by 10 microM colchicine did not block NE-induced cPLA(2) translocation to the nuclear envelope. CD and LA did not inhibit NE-induced increase in cytosolic calcium and cPLA(2) activity, determined from the hydrolysis of l-1-[(14)C]arachidonyl phosphatidylcholine and release of AA. Coimmunoprecipitation studies showed an association of actin with cPLA(2), which was not altered by CD or LA. Far-Western analysis showed that cPLA(2) interacts directly with actin. Our data suggest that NE-induced cPLA(2) translocation to the nuclear envelope requires an intact actin but not microtubule filaments and that cPLA(2) phosphorylation and activation and AA release are independent of its translocation to the nuclear envelope in rabbit VSMCs.

Actins↗

PubMed1987

Dietary butylated hydroxytoluene protects cytochrome P-450 in hepatic nuclear membranes of rats fed 2-acetylaminofluorene.

We previously reported that during hepatocarcinogenesis which is induced by feeding 2-acetylaminofluorene (AAF) there is an early loss of cytochrome P-450 in the nuclear envelope (Carubelli et al., Chem. Biol. Interact. 58, 125-136, 1986). Cytochrome P-450 participates in the activation in addition to the detoxification of xenobiotics; therefore, these findings suggested that AAF may cause the loss of an important defense for the protection of the genetic material of the nucleus against carcinogenic metabolites of AAF generated by microsomal P-450 which, in contrast to the nuclear envelope cytochrome P-450, remains essentially undiminished during early stages of AAF feeding. Because dietary butylated hydroxytoluene (BHT) affords good protection against AAF carcinogenicity, we decided to investigate the possibility that the BHT effect could be mediated through the preservation of nuclear envelope cytochrome P-450. AAF (0.05% wt/wt) was administered in a purified diet with a high content of polyunsaturated fat (20% wt/wt corn oil), which is known to enhance AAF carcinogenicity. These studies showed that BHT supplementation (0.3% wt/wt) of control in addition to the AAF-containing diets resulted in higher levels of nuclear envelope cytochrome P-450. After 16 weeks of AAF feeding, nuclear envelope cytochrome P-450 could not be detected in rats fed BHT-free diet, whereas in the rats fed the diet containing AAF and BHT, measurable amounts of nuclear envelope P-450 were observed. These results are compatible with the hypothesis that nuclear envelope cytochrome P-450 is needed for protection against AAF and that BHT protects nuclear envelope cytochrome P-450.

2-Acetylaminofluorene↗

PubMed2002

Functional domains of the nucleus: implications for Emery-Dreifuss muscular dystrophy.

Elucidation of the pathophysiology of Emery-Dreifuss muscular dystrophy, caused by mutations in emerin or lamin A/C, will require deciphering the role of these proteins in the functional organization of the nuclear envelope. This review focuses on nuclear envelope related mechanisms that modulate chromatin arrangement and control of gene transcription, both potential targets of the disease process in Emery-Dreifuss muscular dystrophy. Interactions of these proteins with chromatin- and nuclear matrix-associated proteins are now of particular interest, since chromatin alterations occur in cells in Emery-Dreifuss muscular dystrophy. Both emerin and lamin A/C interact with nuclear actin, a component of the chromatin remodeling complex associated with the nuclear matrix, suggesting that either chromatin arrangement, or gene transcription, or both, might be impaired in the disease.

Animals↗

PubMed1998

Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope-ER network in yeast.

26S proteasomes are the key enzyme complexes responsible for selective turnover of short-lived and misfolded proteins. Based on the assumption that they are dispersed over the nucleoplasm and cytoplasm in all eukaryotic cells, we wanted to determine the subcellular distribution of 26S proteasomes in living yeast cells. For this purpose, we generated yeast strains that express functional green fluorescent protein (GFP) fusions of proteasomal subunits. An alpha subunit of the proteolytically active 20S core complex of the 26S proteasome, Pre6/YOL038w, as well as an ATPase-type subunit of the regulatory 19S cap complex, Cim5/YOL145w, were tagged with GFP. Both chimeras were shown to be incorporated completely into active 26S proteasomes. Microscopic analysis revealed that GFP-labelled 20S as well as 19S subunits are accumulated mainly in the nuclear envelope (NE)-endoplasmic reticulum (ER) network in yeast. These findings were supported by the co-localization and co-enrichment of 26S proteasomes with NE-ER marker proteins. A major location of proteasomal peptide cleavage activity was visualized in the NE-ER network, indicating that proteasomal degradation takes place mainly in this subcellular compartment in yeast.

Adenosine Triphosphatases↗

PubMed1992

Nuclear membrane modifications in polytene nuclei of Drosophila melanogaster: serial reconstruction and cytochemistry.

The nuclear envelope of polytene nuclei of salivary glands of Drosophila melanogaster displays modifications consisting of nuclear envelope invaginations (NEI) and evaginations (NEE). Ultrastructural analyses combined with three-dimensional reconstruction and cytochemistry show that NEI are bounded by a single membrane and that they may arise as invaginations of the inner nuclear membrane. NEI extend deeply into the nucleus. The lumens of NEI may collapse resulting in membranous sheets which may combine with those arising from adjacent NEI to form intranuclear structures resembling annulate lamellae. All NEI are associated with NEE. In contrast to NEI, NEE are enclosed in a double membrane morphologically identical to the nuclear envelope. While NEI and NEE share wheat germ agglutinin binding properties with the nuclear envelope, they differ in their ability to localize lanthanum. Pore annuli of NEI display complete lack of lanthanum binding, while those of NEE exhibit minor deposition of this cation. In contrast, pore annuli of the nuclear envelope are specifically and significantly decorated by lanthanum. A conceptual model based on the results obtained suggests that NEI are formed by invaginations of the inner nuclear membrane, together with accompanying modifications of pore complexes.

Animals↗

PubMed1994

Insertional mutation that causes acrosomal hypo-development: its relationship to sperm head shaping.

A family of transgenic mice (OVE 219) was generated by microinjection of a tyrosinase minigene (Ty811C). The transgenic mice demonstrate an atypical and variable coat color pattern and the homozygous males show abnormalities of spermatogenesis that are variably expressed from animal to animal. Heterozygous mice proved to have normal spermatogenesis and along with non-transgenic mice were used as controls to study the abnormalities in spermatogenesis in OVE 219 homozygous males. These abnormalities shed light on the features controlling normal spermatogenesis. In some homozygous males early spermiogenesis was disrupted as the flagellar microtubules became disorganized within the flagellar process. What appeared to be crystalline tubulin was noted within some of the rounded flagellar processes. Sperm with this defect did not develop a flagellum. In other homozygous males defects were apparent by step 6 or 7 of spermiogenesis when the acrosome did not grow and spread over the nucleus as noted in control animals. The modified nuclear envelope underlying the acrosome continued to develop and spread well beyond one margin of the acrosome. Since the modified nuclear envelope grew independently of the acrosome, the acrosome was not the controlling factor in determining the spread of the modified nuclear envelope. Micrographs revealed that Sertoli ectoplasmic specialization failed to form over most regions of the spermatid head lacking a normal acrosome. In homozygous males, the manchette took origin (proximally) in close relation to the modified nuclear envelope and never in relation to the edge of the spreading acrosome, a feature indicating that manchette placement was influenced by the position of the modified nuclear envelope and not the edge of the acrosome. Thus the modification in the nuclear envelope may be the primary event to signal acrosomal spread and manchette development. In spermatids where the manchette developed from an ectopic site, the result was abnormal caudal head shaping. In some spermatids a portion of the manchette was lacking. When this occurred the caudal head was rounded in the region of the missing manchette. In a minority of spermatids there was no evidence for a manchette. The entire caudal head was gently rounded. These data support the growing body of evidence that the caudal sperm head is shaped, in part, by the manchette. The OVE 219 family of mice provides a useful model to understand the processes involved in periods of spermiogenesis that are critical to development of a normally shaped sperm head.

Acrosome↗

PubMed2005

Dissociation of heterochromatin protein 1 from lamin B receptor induced by human polyomavirus agnoprotein: role in nuclear egress of viral particles.

The nuclear envelope is one of the chief obstacles to the translocation of macromolecules that are larger than the diameter of nuclear pores. Heterochromatin protein 1 (HP1) bound to the lamin B receptor (LBR) is thought to contribute to reassembly of the nuclear envelope after cell division. Human polyomavirus agnoprotein (Agno) has been shown to bind to HP1alpha and to induce its dissociation from LBR, resulting in destabilization of the nuclear envelope. Fluorescence recovery after photobleaching showed that Agno increased the lateral mobility of LBR in the inner nuclear membrane. Biochemical and immunofluorescence analyses showed that Agno is targeted to the nuclear envelope and facilitates the nuclear egress of polyomavirus-like particles. These results indicate that dissociation of HP1alpha from LBR and consequent perturbation of the nuclear envelope induced by polyomavirus Agno promote the translocation of virions out of the nucleus.

Active Transport, Cell Nucleus↗

PubMed1991

Nuclear transplantation in bovine embryo: fine structural and autoradiographic studies.

Nucleolar fine structure, "blebbing" activity of nuclear envelope, and activation of heterogeneous nuclear RNA (hnRNA) synthesis were studied in bovine reconstructed embryos obtained by electrofusion of a single eight-cell blastomere with an enucleated oocyte. Developmental progress of nucleolar fine structure and hnRNA synthesis are arrested during three cell cycles following fusion. The activation of both appears during the eight-cell stage of the reconstructed embryo, after the same number of cell cycles after fusion as in nonmanipulated bovine embryos after fertilization. "Blebbing" activity of nuclear envelope, which is already absent in original blastomeres, reappears after fusion and continues for the next two cell cycles. From the present results, it can be concluded that the donor nuclei are arrested after fusion in morphology and function. Their reactivation corresponds to the developmental pattern typical for normal bovine embryos.

Animals↗

PubMed1983

Nuclear ribonucleoprotein release and nucleoside triphosphatase activity are inhibited by antibodies directed against one nuclear matrix glycoprotein.

Circumstantial evidence suggests that nucleocytoplasmic exchange or transport is an active process involving the nuclear pore complex of the nuclear envelope. To test this hypothesis, antibodies were generated against nuclear envelope components from a highly enriched pore complex fraction from Spisula solidissima oocytes. Some of these antibodies inhibited ATP-dependent ribonucleoprotein release from prelabeled, isolated rat nuclei and inhibited nucleoside triphosphatase activity essential in nucleocytoplasmic transport. Inhibition of both functions by lectins indicated that the antigen was a glycoprotein. It was identified as lamin B, a major component of the nuclear envelope and nuclear matrix. This glycoprotein may not only be a structural nuclear protein but also may have nucleoside triphosphatase activity. We speculate that lamin B represents the solid support for ribonucleoprotein transport. This protein is expected to be highly conserved if active transport in and out of the nucleus is essential in the eukaryotic system.

Adenosine Triphosphate↗

PubMed2006

Topology of yeast Ndc1p: predictions for the human NDC1/NET3 homologue.

The nuclear pore complex is the predominant structure in the nuclear envelope that spans the double nuclear membranes of all eukaryotes. Yeasts have one additional organelle that is also embedded in the nuclear envelope: the spindle pole body, which functions as the microtubule organizing center. The only protein known to localize to and be important in the assembly of both of these yeast structures is the integral membrane protein, Ndc1p. However, no homologues of Ndc1p had been characterized in metazoa. Here, we identify and analyze NDC1 homologues that are conserved throughout evolution. We show that the overall topology of these homologues is conserved. Each contains six transmembrane segments in its N-terminal half and has a large soluble C-terminal half of approximately 300 amino acids. Charge distribution analysis infers that the N- and C-termini are exposed to the cytoplasm. Limited proteolysis of yeast Ndc1p in cellular membranes confirms the orientation of its C-terminus. Although it is not known whether vertebrate NDC1 protein localizes to nuclear pores like its yeast counterpart, the human homologue contains three FG repeats in the C-terminus, a feature of many nuclear pore proteins. Moreover, a small region containing mutations that affect assembly of the nuclear pore in yeast is highly conserved throughout evolution. Lastly, we bring together data from another study to demonstrate that the human homologue of NDC1 is the known inner nuclear membrane protein, NET3.

Amino Acid Sequence↗