Abstract
Reticulons (RTNs) are a large family of membrane associated proteins with various functions. NOGO-A/RTN4A has a well-known function in limiting neurite outgrowth and restricting the plasticity of the mammalian central nervous system. On the other hand, Reticulon 4 proteins were shown to be involved in forming and maintaining endoplasmic reticulum (ER) tubules. Using comparative transcriptome analysis and qPCR, we show here that NOGO-B/RTN4B and NOGO-A/RTN4A are simultaneously expressed in cultured epithelial, fibroblast and neuronal cells. Electron tomography combined with immunolabelling reveal that both isoforms localize preferably to curved membranes on ER tubules and sheet edges. Morphological analysis of cells with manipulated levels of NOGO-B/RTN4B revealed that it is required for maintenance of normal ER shape; over-expression changes the sheet/tubule balance strongly towards tubules and causes the deformation of the cell shape while depletion of the protein induces formation of large peripheral ER sheets.
Highlights
Two members of reticulon (RTN) family, NOGO-A/RTN4A and NOGO-B/RTN4B, have recently been the focus of intense investigation due to their functions as an inhibitor of neurite outgrowth and involvement in restricting the plasticity of the central nervous system[1,2,3] and on the other hand, in generating curvature on endoplasmic reticulum (ER) tubules[4]
Authors suggested that the hydrophobic regions of reticulon homology domain may form two hairpin loops that are wedged into the outer membrane leaflet, creating the necessary increase in local surface area needed for high membrane curvature
Our immuno-EM studies could not verify these findings as no labelling was observed on the extracellular side of the plasma membrane (PM). These results indicate that NOGO-A/RTN4A and NOGO-B/RTN4B both localize prominently on ER tubules and sheet edges
Summary
Two members of reticulon (RTN) family, NOGO-A/RTN4A and NOGO-B/RTN4B, have recently been the focus of intense investigation due to their functions as an inhibitor of neurite outgrowth and involvement in restricting the plasticity of the central nervous system[1,2,3] and on the other hand, in generating curvature on ER tubules[4]. The discrepancy between these findings comes from the required localization and topology of membrane insertion needed to support these functions. Atlastin has been shown to bind to ATPase spastin[16] that interacts with RTN117
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