Abstract
The nucleus-initiated augmentation of ER membrane is reflected in a coordinated synthesis and intercalation of the explicit proteins and lipids required for the replacement, repair and function of the cell and its organelles. The direct connection between nucleus and the membranes containing labeled sphingosine (SphN) and ceramide (Cer) was affirmed by determining synthetic activity of serine palmitoyltransferase (SPT). The SPT and the newly synthesized serine-labeled lipid products were identified in the Outer- and Inner-Nuclear Membrane (ONM, INM) and ER. The pulse-chase experiments disclosed that the incorporation of radiolabeled lipids into both nuclear membranes declined upon their simultaneous increase in Endoplasmic Reticulum (ER). These results, and prior findings regarding metabolic transfer of nuclear membrane phosphoinositides to the outer leaflet of ER [Slomiany and Slomiany, Health, 2011, 3, 187-199], allowed us to reason that INM and ONM are not distinct entities, but uninterrupted continuum facing nucleosol and then cytosol when protracted into segment known as ER. Consequently, the identification of SPT and its products in the inner leaflet of nuclear and ER microsomes lent credence to the luminal presence of Cer in Golgi, luminal synthesis of glycosphingolipids (GSphLs), sphingomyelin (SM), and their delivery to the outer leaflet of apical and basolateral cell membrane, respectively. The findings presented in this communication provide further support to our concept that the factual intercalation of proteins and lipids into the cell membranes can only take place during their simultaneous synthesis that is guided by the nuclear and cytosolic processes enacted in nuclear-ER membrane continuum. At the nuclear stage, the signal-specific genes expression promotes active synthesis and intercalation of lipids into the organelles’ customized membrane that is protracted and articulated in ER in form of transport vesicles.
Highlights
The nuclear envelope is viewed as a double bilayer membrane barrier, the entity separating and yet fully linking nuclear and cytoplasmic processes that promote and impact cellular physiological functions and organelles’ and cell’s restitution [1] [2] [3]
While our study revealed that Endoplasmic Reticulum (ER) microsomes produce variety of transport vesicles whose lipid composition and appearance of the leaflet-lipid specificity defines their delivery to Golgi or Mitochondria [26] [27] [28] [29] [30], here we have investigated contribution of the nucleus-retained nuclear microsomes on the synthesis of the membranes referred in literature as Outer- and Inner Nuclear Membrane (ONM and INM)
Underpinning for our hypothesis that the nuclear barrier is built of single bilayer membrane that embodies uninterrupted continuum with ER emerged during investigations of inositol phosphatides transformation culminating in synthesis of nuclear membrane phosphatidylinositol (PI) and its passage to ER [27]
Summary
The nuclear envelope is viewed as a double bilayer membrane barrier, the entity separating and yet fully linking nuclear and cytoplasmic processes that promote and impact cellular physiological functions and organelles’ and cell’s restitution [1] [2] [3]. The knowledge regarding this phenomenon is extensive but its main focus on proteins and molecular transport crisscrossing envelope via nuclear pores generates incomplete and unfounded portrayal of the event [4] [5] [6]. The scheme of nuclear membrane function in the assembly of cell structures, without parallel emphasis on lipid involvement in the completion of the signal-induced processes remains incomplete, dimensionless and static
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