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In this report, the authors present evidence on the restitution of nuclear …

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- Homeostatic restitution of cell membranes. Nuclear membrane lipid biogenesis and transport of protein from cytosol to intranuclear spaces

1. Introduction

Transcriptome informs which genes are induced or repressed by the metabolic and physical status of the cell, but does not generate the roadmap that illustrates cellular homeostatic restitutions, or cellular changes leading to transformation. The largest void in the understanding of cellular signaling is created by an inadequate presentation of the correct spatial organization of all molecules that are crucial in carrying signals and traversing cellular, organellar, and nuclear membranes [1,2-5]. The general information on protein structure and modification is insufficient to explain when the protein traverses cellular membranes and uniquely intercalates into the membrane, but merely indicates potential to associate with outer- or inner membranous surface. While hydrophobic and hydrophilic domains of the protein indicate its native intra-membrane placement, the information on how and when the protein is placed within specialized membrane, or its intercalation into the specific membrane domain is assured remains unknown [6-9]. Hence, the quintessential event of the protein insertion into exact site of cellular membrane that governs fidelity of the homeostatic processes has not been identified [1, 6-9]. In the investigative paradigms of proteome, the studies also bypass the relevance of cell compartmentalization with specific membrane systems, the different rate of cellular compartments restitution and the significance of signal translation within the spaces delimited by membranous networks. Consequently, we only know that the genome responds to extracellular signals, the concentration of transcription factors, and that the rate of protein production and deposition in the specific sites or cell compartments must be ceaselessly reproduced [1,7-10].

In the terminally differentiated epithelial cell, the secretory activity of the apical surface of the cell requires steady and precise regeneration of cellular organelles, nucleus and the cell membrane. Thus, to sustain the designated and functional structure of the cell, the processes are engaged that generate new membranes and catabolize the membrane that is modified by signal-induced receptors [5,11-19]. Yet, this fundamental aspect of the whole cell reassembly is not investigated, and the synthesis of cellular membranes is presumed as deposition of native or extraneous lipids from cytosol, or the intracellular retrieval of the membranous transporters after release of the secretory cargo [7,8,20-26]. The provisional assumptions of the cell membranes regeneration are not challenged or argued that such processes would create indistinguishable cellular membranes, and not the membranes that provide discretely dissimilar profile for each intracellular organelle. Moreover, the receptors affinity to membrane due to hydrophobic amino acid sequence in the protein is also presumed as sufficient argument for the receptor intercalation into the membrane [20,23,27]. Hence, when the intercalation of membrane receptors takes place is not pursued.

Our investigations on biomembrane biogenesis concentrate on the initiation and restitution of the cellular membranes and provides evidence that in endoplasmic reticulum (ER), the membrane lipids and the specific membrane protein are intercalated and as ER transport vesicles delivered en bloc to Golgi [13-18]. In Golgi, the maturation/modification of the membrane ensures distinct composition of the transport vesicles that restore original proteins and lipids in Golgi, endosomes, and apical cell membrane [16-18]. In this report, we present evidence on the restitution of nuclear membranes which proceeds through the synthesis of lipids in the outer nuclear/ER membrane, and hypothesize that such a course of events is connected to the restitution of the inner nuclear membrane, transport of the cytosol-contained protein to nucleus, and the restitution of ER membrane. The finding that cell cytosol impacts organelle and nuclear membrane restitution provides important clue for designing media to redirect, impact or control cell growth, differentiation, and transformation.

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