925 research outputs found
Two different subunits of importin cooperate to recognize nuclear localization signals and bind them to the nuclear envelope
AbstractBackground: Selective protein import into the cell nucleus occurs in two steps: binding to the nuclear envelope, followed by energy-dependent transit through the nuclear pore complex. A 60 kD protein, importin, is essential for the first nuclear import step, and the small G protein Ran/TC4 is essential for the second. We have previously purified the 60 kD importin protein (importin 60) as a single polypeptide.Results We have identified importin 90, a 90 kD second subunit that dissociates from importin 60 during affinity chromatography on nickel (II)–nitrolotriacetic acid–Sepharose, a technique that was originally used to purify importin 60. Partial amino-acid sequencing of Xenopus importin 90 allowed us to clone and sequence its human homologue; the amino-acid sequence of importin 90 is strikingly conserved between the two species. We have also identified a homologous budding yeast sequence from a database entry. Importin 90 potentiates the effects of importin 60 on nuclear protein import, indicating that the importin complex is the physiological unit responsible for import. To assess whether nuclear localization sequences are recognized by cytosolic receptor proteins, a biotin-tagged conjugate of nuclear localization signals linked to bovine serum albumin was allowed to form complexes with cytosolic proteins in Xenopus egg extracts; the complexes were then retrieved with streptavidin–agarose. The pattern of bound proteins was surprisingly simple and showed only two predominant bands: those of the importin complex. We also expressed the human homologue of importin 60, Rch1p, and found that it was able to replace its Xenopus counterpart in a functional assay. We discuss the relationship of importin 60 and importin 90 to other nuclear import factors.Conclusion Importin consists of a 60 and a 90 kD subunit. Together, they constitute a cytosolic receptor for nuclear localization signals that enables import substrates to bind to the nuclear envelope
Five-brane Instantons vs Flux-induced Gauging of Isometries
In five-dimensional heterotic M-theory there is necessarily nonzero
background flux, which leads to gauging of an isometry of the universal
hypermultiplet moduli space. This isometry, however, is poised to be broken by
M5-brane instanton effects. We show that, similarly to string theory, the
background flux allows only brane instantons that preserve the above isometry.
The zero-mode counting for the M5 instantons is related to the number of
solutions of the Dirac equation on their worldvolume. We investigate that
equation in the presence of generic background flux and also, in a particular
case, with nonzero worldvolume flux.Comment: 27 pages; reference adde
Interaction between NTF2 and xFxFG-containing nucleoporins is required to mediate nuclear import of RanGDP.
Nuclear transport factor 2 (NTF2) is a small, homodimeric protein that binds to both RanGDP and xFxFG repeat-containing nucleoporins, such as yeast Nsp1p and vertebrate p62. NTF2 is required for efficient nuclear protein import and has been shown to mediate the nuclear import of RanGDP. We have used the crystal structures of rat NTF2 and its complex with RanGDP to design a mutant, W7A-NTF2, in which the affinity for xFxFG-repeat nucleoporins is reduced while wild-type binding to RanGDP is retained. The 2.5 Å resolution crystal structure of W7A-NTF2 is virtually superimposable upon the wild-type protein structure, indicating that the mutation had not introduced a more general conformational change. Therefore, our data suggest that the exposed side-chain of residue 7 is crucial to the interaction between NTF2 and xFxFG repeat-containing nucleoporins. Consistent with its reduced affinity for xFxFG nucleoporins, fluorescently labelled W7A-NTF2 binds less strongly to the nuclear envelope of permeabilized cultured cells than wild-type NTF2 and, when microinjected into Xenopus oocytes, colloidal gold coated with W7A-NTF2 binds less strongly to the central channel of nuclear pore complexes than wild-type NTF2-coated gold. Significantly, W7A-NTF2 only weakly stimulated the nuclear import of fluorescein-labelled RanGDP, providing direct evidence that an interaction between NTF2 and xFxFG repeat-containing nucleoporins is required to mediate the nuclear import of RanGDP
Counting fermionic zero modes on M5 with fluxes
We study the Dirac equation on an M5 brane wrapped on a divisor in a
Calabi--Yau fourfold in the presence of background flux. We reduce the
computation of the normal bundle U(1) anomaly to counting the solutions of a
finite--dimensional linear system on cohomology. This system depends on the
choice of flux. In an example, we find that the presence of flux changes the
anomaly and allows instanton corrections to the superpotential which would
otherwise be absent.Comment: 14 pages. v2: reference added, typos corrected, few change
Geometry of the quantum universe
A universe much like the (Euclidean) de Sitter space-time appears as
background geometry in the causal dynamical triangulation (CDT) regularization
of quantum gravity. We study the geometry of such universes which appear in the
path integral as a function of the bare coupling constants of the theory.Comment: 19 pages, 7 figures. Typos corrected. Conclusions unchange
The Nonperturbative Quantum de Sitter Universe
The dynamical generation of a four-dimensional classical universe from
nothing but fundamental quantum excitations at the Planck scale is a
long-standing challenge to theoretical physicists. A candidate theory of
quantum gravity which achieves this goal without invoking exotic ingredients or
excessive fine-tuning is based on the nonperturbative and
background-independent technique of Causal Dynamical Triangulations. We
demonstrate in detail how in this approach a macroscopic de Sitter universe,
accompanied by small quantum fluctuations, emerges from the full gravitational
path integral, and how the effective action determining its dynamics can be
reconstructed uniquely from Monte Carlo data. We also provide evidence that it
may be possible to penetrate to the sub-Planckian regime, where the Planck
length is large compared to the lattice spacing of the underlying
regularization of geometry.Comment: Article unchanged. Line added in acknowledgmen
Stringy Instantons and Cascading Quivers
D-brane instantons can perturb the quantum field theories on space-time
filling D-branes by interesting operators. In some cases, these D-brane
instantons are novel "stringy" effects (not interpretable directly as instanton
effects in the low-energy quantum field theory), while in others the D-brane
instantons can be directly interpreted as field theory effects. In this note,
we describe a situation where both perspectives are available, by studying
stringy instantons in quivers which arise at simple Calabi-Yau singularities.
We show that a stringy instanton which wraps an unoccupied node of the quiver,
and gives rise to a non-perturbative mass in the space-time field theory, can
be reinterpreted as a conventional gauge theory effect by going up in an
appropriate renormalization group cascade. Interestingly, in the cascade, the
contribution of the stringy instanton does not come from gauge theory
instantons but from strong coupling dynamics.Comment: 17 pages, 6 figures, harvma
Wrapped Magnetized Branes: Two Alternative Descriptions?
We discuss two inequivalent ways for describing magnetized D-branes wrapped N
times on a torus T^2. The first one is based on a non-abelian gauge bundle
U(N), while the second one is obtained by means of a Narain T-duality
transformation acting on a theory with non-magnetized branes. We construct in
both descriptions the boundary state and the open string vertices and show that
they give rise to different string amplitudes. In particular, the description
based on the gauge bundle has open string vertex operators with momentum
dependent Chan-Paton factors.Comment: 60 pages, LaTe
D3 Brane Action and Fermion Zero Modes in Presence of Background Flux
We derive the fermion bilinear terms in the world volume action for a D3
brane in the presence of background flux. In six-dimensional compactifications
non-perturbative corrections to the superpotential can arise from an Euclidean
D3-brane instanton wrapping a divisor in the internal space. The bilinear terms
give rise to fermion masses and are important in determining these corrections.
We find that the three-form flux generically breaks a U(1) subgroup of the
structure group of the normal bundle of the divisor. In an example of
compactification on T^6/Z_2, six of the sixteen zero modes originally present
are lifted by the flux.Comment: Important factor of ``i'' was overlooked in Euclidean continuation of
WZ term. This changes the count of zero-modes in the T^6/Z_2 example. Main
result stays unchanged. We thank Bergshoeff, Kallosh, Kashani-Poor, Sorokin
and Tomasiello for pointing this ou
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