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Physiol. Rev. 81: 1-19, 2001;
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Physiological Reviews, Vol. 81, No. 1, January 2001, pp. 1-19
Copyright ©2001 by the American Physiological Society

Electrical Dimension of the Nuclear Envelope

Michele Mazzanti, José Omar Bustamante, and Hans Oberleithner

Dipartmento di Biologia Cellulare e dello Sviluppo, Università "la Sapienza," Rome, Italy; Nuclear Physiology Lab, University Tiradentes, Aracaju, Sergipe, Brazil; and Department of Physiology, University of Münster, Münster, Germany

Mazzanti, Michele, José Omar Bustamante, and Hans Oberleithner. Electrical Dimension of the Nuclear Envelope. Physiol. Rev. 81: 1-19, 2001.Eukaryotic chromosomes are confined to the nucleus, which is separated from the rest of the cell by two concentric membranes known as the nuclear envelope (NE). The NE is punctuated by holes known as nuclear pore complexes (NPCs), which provide the main pathway for transport of cellular material across the nuclear-cytoplasmic boundary. The single NPC is a complicated octameric structure containing more than 100 proteins called nucleoporins. NPCs function as transport machineries for inorganic ions and macromolecules. The most prominent feature of an individual NPC is a large central channel, ~7 nm in width and 50 nm in length. NPCs exhibit high morphological and functional plasticity, adjusting shape to function. Macromolecules ranging from 1 to >100 kDa travel through the central channel into (and out of) the nucleoplasm. Inorganic ions have additional pathways for communication between cytosol and nucleus. NE can turn from a simple sieve that separates two compartments by a given pore size to a smart barrier that adjusts its permeabiltiy to the metabolic demands of the cell. Early microelectrode work characterizes the NE as a membrane barrier of highly variable permeability, indicating that NPCs are under regulatory control. Electrical voltage across the NE is explained as the result of electrical charge separation due to selective barrier permeability and unequal distribution of charged macromolecules across the NE. Patch-clamp work discovers NE ion channel activity associated with NPC function. From comparison of early microelectrode work with patch-clamp data and late results obtained by the nuclear hourglass technique, it is concluded that NPCs are well-controlled supramolecular structures that mediate transport of macromolecules and small ions by separate physical pathways, the large central channel and the small peripheral channels, respectively. Electrical properties of the two pathways are still unclear but could have great impact on the understanding of signal transfer across NE and gene expression.




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