Abstract
The mechanisms that coordinately regulate lipid synthesis in the nervous system together with the high rates of membrane biogenesis needed to support cell growth are largely unknown as are their subcellular site of synthesis. c-Fos, a well-known AP-1 transcription factor, has emerged as a unique protein with the capacity to associate to specific enzymes of the pathway of synthesis of phospholipids at the endoplasmic reticulum and activate their synthesis to accompany genomic decisions of growth. Herein, we discuss this effect of c-Fos in the context of neuronal differentiation and also with respect to pathologies of the nervous system such as the development and growth of tumors. We also provide insights into the sub-cellular sites where this regulation occurs at the endoplasmic reticulum membranes and the molecular mechanism by which c-Fos exerts this activity.
Highlights
Lipids, essential constituent molecules of all organisms, participate in a broad range of cellular processes
The homeostasis of the lipid content of the nervous system is of vital importance, since several neuropathologies have been associated to their abnormal metabolism (Ahmed et al, 2017; Gaspar et al, 2018; Valadas et al, 2018; Yu et al, 2018)
We found that at the endoplasmic reticulum (ER), c-Fos is capable of activating only some particular enzymes of the different lipid synthetizing pathways: CDPdiacylglycerolsynthase-1 (CDS1), Phosphatidylinositol-4-kinase type II α (PI4KIIα) and Lipin-1 are activated by c-Fos, whereas Phosphatidylinositol synthase (PIS1) and Phosphatidylinositol4-kinase type II β (PI4KIIβ) are not (Alfonso Pecchio et al, 2011; Cardozo Gizzi et al, 2015)
Summary
C-Fos, a well-known AP1 transcription factor, has emerged as a unique protein with the capacity to associate to specific enzymes of the pathway of synthesis of phospholipids at the endoplasmic reticulum and activate their synthesis to accompany genomic decisions of growth. We discuss this effect of c-Fos in the context of neuronal differentiation and with respect to pathologies of the nervous system such as the development and growth of tumors. We provide insights into the sub-cellular sites where this regulation occurs at the endoplasmic reticulum membranes and the molecular mechanism by which c-Fos exerts this activity
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