856 research outputs found
The CaVβ Subunit Protects the I-II Loop of the Voltage-gated Calcium Channel CaV2.2 from Proteasomal Degradation but Not Oligoubiquitination.
CaVβ subunits interact with the voltage-gated calcium channel CaV2.2 on a site in the intracellular loop between domains I and II (the I-II loop). This interaction influences the biophysical properties of the channel and leads to an increase in its trafficking to the plasma membrane. We have shown previously that a mutant CaV2.2 channel that is unable to bind CaVβ subunits (CaV2.2 W391A) was rapidly degraded (Waithe, D., Ferron, L., Page, K. M., Chaggar, K., and Dolphin, A. C. (2011) J. Biol. Chem. 286, 9598-9611). Here we show that, in the absence of CaVβ subunits, a construct consisting of the I-II loop of CaV2.2 was directly ubiquitinated and degraded by the proteasome system. Ubiquitination could be prevented by mutation of all 12 lysine residues in the I-II loop to arginines. Including a palmitoylation motif at the N terminus of CaV2.2 I-II loop was insufficient to target it to the plasma membrane in the absence of CaVβ subunits even when proteasomal degradation was inhibited with MG132 or ubiquitination was prevented by the lysine-to-arginine mutations. In the presence of CaVβ subunit, the palmitoylated CaV2.2 I-II loop was protected from degradation, although oligoubiquitination could still occur, and was efficiently trafficked to the plasma membrane. We propose that targeting to the plasma membrane requires a conformational change in the I-II loop that is induced by binding of the CaVβ subunit
The information paradox: conflicts and resolutions
Many relativists have been long convinced that black hole evaporation leads
to information loss or remnants. String theorists have however not been too
worried about the issue, largely due to a belief that the Hawking argument for
information loss is flawed in its details. A recently derived inequality shows
that the Hawking argument for black holes with horizon can in fact be made
rigorous. What happens instead is that in string theory black hole microstates
have no horizons. Thus the evolution of radiation quanta with E ~ kT is
modified by order unity at the horizon, and we resolve the information paradox.
We discuss how it is still possible for E >> kT objects to see an approximate
black hole like geometry. We also note some possible implications of this
physics for the early Universe.Comment: 26 pages, 8 figures, Latex; (Expanded version of) proceedings for
Lepton-Photon 201
Black Hole Emission in String Theory and the String Phase of Black Holes
String theory properly describes black-hole evaporation. The quantum string
emission by Black Holes is computed. The black-hole temperature is the Hawking
temperature in the semiclassical quantum field theory (QFT) regime and becomes
the intrinsic string temperature, T_s, in the quantum (last stage) string
regime. The QFT-Hawking temperature T_H is upper bounded by the string
temperature T_S. The black hole emission spectrum is an incomplete gamma
function of (T_H - T_S). For T_H << T_S, it yields the QFT-Hawking emission.
For T_H \to T_S, it shows highly massive string states dominate the emission
and undergo a typical string phase transition to a microscopic `minimal' black
hole of mass M_{\min} or radius r_{\min} (inversely proportional to T_S) and
string temperature T_S. The string back reaction effect (selfconsistent black
hole solution of the semiclassical Einstein equations) is computed. Both, the
QFT and string black hole regimes are well defined and bounded.The string
`minimal' black hole has a life time tau_{min} simeq (k_B c)/(G hbar [T_S]^3).
The semiclassical QFT black hole (of mass M and temperature T_H) and the string
black hole (of mass M_{min} and temperature T_S) are mapped one into another by
a `Dual' transform which links classical/QFT and quantum string regimes.Comment: LaTex, 22 pages, Lectures delivered at the Chalonge School, Nato ASI:
Phase Transitions in the Early Universe: Theory and Observations. To appear
in the Proceedings, Editors H. J. de Vega, I. Khalatnikov, N. Sanchez.
(Kluwer Pub
Accretion, Primordial Black Holes and Standard Cosmology
Primordial Black Holes evaporate due to Hawking radiation. We find that the
evaporation time of primordial black holes increase when accretion of radiation
is included.Thus depending on accretion efficiency more and more number of
primordial black holes are existing today, which strengthens the idea that the
primordial black holes are the proper candidate for dark matter.Comment: 11 pages, 3 figure
CPT Violation, Strings, and Neutral-Meson Systems
This talk provides a short overview of recent results on possible CPT
violation and some associated experimental signatures.Comment: Presented at Orbis Scientiae, January 199
Quantum Back Reaction to asymptotically AdS Black Holes
We analyze the effects of the back reaction due to a conformal field theory
(CFT) on a black hole spacetime with negative cosmological constant. We study
the geometry numerically obtained by taking into account the energy momentum
tensor of CFT approximated by a radiation fluid. We find a sequence of
configurations without a horizon in thermal equilibrium (CFT stars), followed
by a sequence of configurations with a horizon. We discuss the thermodynamic
properties of the system and how back reaction effects alter the space-time
structure. We also provide an interpretation of the above sequence of solutions
in terms of the AdS/CFT correspondence. The dual five-dimensional description
is given by the Karch-Randall model, in which a sequence of five-dimensional
floating black holes followed by a sequence of brane localized black holes
correspond to the above solutions.Comment: 13 pages, 10 figure
The holographic principle
There is strong evidence that the area of any surface limits the information
content of adjacent spacetime regions, at 10^(69) bits per square meter. We
review the developments that have led to the recognition of this entropy bound,
placing special emphasis on the quantum properties of black holes. The
construction of light-sheets, which associate relevant spacetime regions to any
given surface, is discussed in detail. We explain how the bound is tested and
demonstrate its validity in a wide range of examples.
A universal relation between geometry and information is thus uncovered. It
has yet to be explained. The holographic principle asserts that its origin must
lie in the number of fundamental degrees of freedom involved in a unified
description of spacetime and matter. It must be manifest in an underlying
quantum theory of gravity. We survey some successes and challenges in
implementing the holographic principle.Comment: 52 pages, 10 figures, invited review for Rev. Mod. Phys; v2:
reference adde
An Exact Formula for the Average Run Length to False Alarm of the Generalized Shiryaev-Roberts Procedure for Change-Point Detection under Exponential Observations
We derive analytically an exact closed-form formula for the standard minimax
Average Run Length (ARL) to false alarm delivered by the Generalized
Shiryaev-Roberts (GSR) change-point detection procedure devised to detect a
shift in the baseline mean of a sequence of independent exponentially
distributed observations. Specifically, the formula is found through direct
solution of the respective integral (renewal) equation, and is a general result
in that the GSR procedure's headstart is not restricted to a bounded range, nor
is there a "ceiling" value for the detection threshold. Apart from the
theoretical significance (in change-point detection, exact closed-form
performance formulae are typically either difficult or impossible to get,
especially for the GSR procedure), the obtained formula is also useful to a
practitioner: in cases of practical interest, the formula is a function linear
in both the detection threshold and the headstart, and, therefore, the ARL to
false alarm of the GSR procedure can be easily computed.Comment: 9 pages; Accepted for publication in Proceedings of the 12-th
German-Polish Workshop on Stochastic Models, Statistics and Their
Application
The entropy of black holes: a primer
After recalling the definition of black holes, and reviewing their energetics
and their classical thermodynamics, one expounds the conjecture of Bekenstein,
attributing an entropy to black holes, and the calculation by Hawking of the
semi-classical radiation spectrum of a black hole, involving a thermal
(Planckian) factor. One then discusses the attempts to interpret the black-hole
entropy as the logarithm of the number of quantum micro-states of a macroscopic
black hole, with particular emphasis on results obtained within string theory.
After mentioning the (technically cleaner, but conceptually more intricate)
case of supersymmetric (BPS) black holes and the corresponding counting of the
degeneracy of Dirichlet-brane systems, one discusses in some detail the
``correspondence'' between massive string states and non-supersymmetric
Schwarzschild black holes.Comment: 51 pages, 4 figures, talk given at the "Poincare seminar" (Paris, 6
December 2003), to appear in Poincare Seminar 2003 (Birkhauser
Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking
Voltage-gated calcium channels are exquisitely Ca2+ selective, conferred primarily by four conserved pore-loop glutamate residues contributing to the selectivity filter. There has been little previous work directly measuring whether the trafficking of calcium channels requires their ability to bind Ca2+ in the selectivity filter or to conduct Ca2+. Here, we examine trafficking of neuronal CaV2.1 and 2.2 channels with mutations in their selectivity filter and find reduced trafficking to the cell surface in cell lines. Furthermore, in hippocampal neurons, there is reduced trafficking to the somatic plasma membrane, into neurites, and to presynaptic terminals. However, the CaV2.2 selectivity filter mutants are still influenced by auxiliary α2δ subunits and, albeit to a reduced extent, by β subunits, indicating the channels are not grossly misfolded. Our results indicate that Ca2+ binding in the pore of CaV2 channels may promote their correct trafficking, in combination with auxiliary subunits. Furthermore, physiological studies utilizing selectivity filter mutant CaV channels should be interpreted with caution
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