Regulation of nuclear envelope permeability in cell death and survival

Strasser, Christine; Grote, Patricia; Schäuble, Karin; Ganz, Magdalena; Ferrando-May, Elisa

Regulation of nuclear envelope permeability in cell death and survival

Dateien

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Datum

2012

Autor:innen

Grote, Patricia

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Nucleus. 2012, 3(6), pp. 540-551. ISSN 1949-1034. eISSN 1949-1042. Available under: doi: 10.4161/nucl.21982

Zusammenfassung

The nuclear pore complex (NPC) mediates macromolecular exchange between nucleus and cytoplasm. It is a regulated channel whose functional properties are modulated in response to the physiological status of the cell. Identifying the factors responsible for regulating NPC activity is crucial to understand how intracellular signaling cues are integrated at the level of this channel to control nucleocytoplasmic trafficking. For proteins lacking active translocation signals the NPC acts as a molecular sieve limiting passage across the nuclear envelope (NE) to proteins with a MW below ~40 kD. Here, we investigate how this permeability barrier is altered in paradigms of cell death and cell survival, i.e., apoptosis induction via staurosporine, and enhanced viability via overexpression of Bcl-2. We monitor dynamic changes of the NPC's size-exclusion limit for passive diffusion by confocal time-lapse microscopy of cells undergoing apoptosis, and use different diffusion markers to determine how Bcl-2 expression affects steady-state NE permeability. We show that staurosporine triggers an immediate and gradual leakiness of the NE preceding the appearance of apoptotic hallmarks. Bcl-2 expression leads to a constitutive increase in NE permeability, and its localization at the NE is sufficient for the effect, evincing a functional role for Bcl-2 at the nuclear membrane. In both settings, NPC leakiness correlates with reduced Ca²⁺ in internal stores, as demonstrated by fluorometric measurements of ER/NE Ca²⁺ levels. By comparing two cellular models with opposite outcome these data pinpoint ER/NE Ca²⁺ as a general and physiologically relevant regulator of the permeability barrier function of the NPC.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

STRASSER, Christine, Patricia GROTE, Karin SCHÄUBLE, Magdalena GANZ, Elisa FERRANDO-MAY, 2012. Regulation of nuclear envelope permeability in cell death and survival. In: Nucleus. 2012, 3(6), pp. 540-551. ISSN 1949-1034. eISSN 1949-1042. Available under: doi: 10.4161/nucl.21982

BibTex

@article{Strasser2012-11Regul-22063,
  year={2012},
  doi={10.4161/nucl.21982},
  title={Regulation of nuclear envelope permeability in cell death and survival},
  number={6},
  volume={3},
  issn={1949-1034},
  journal={Nucleus},
  pages={540--551},
  author={Strasser, Christine and Grote, Patricia and Schäuble, Karin and Ganz, Magdalena and Ferrando-May, Elisa}
}

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Universitätsbibliographie

Ja