Nogo-B is associated with cytoskeletal structures in human monocyte-derived macrophages

Abstract

BackgroundThe reticulon Nogo-B participates in cellular and immunological processes in murine macrophages. Since leukocytes are an essential part of the immune system in health and disease, we decided to investigate the expression of Nogo-A, Nogo-B and Nogo-C in different human immune cell subpopulations. Furthermore, we analyzed the localization of Nogo-B in human monocyte-derived macrophages by indirect immunofluorescence stainings to gain further insight into its possible function.FindingsWe describe an association of Nogo-B with cytoskeletal structures and the base of filopodia, but not with focal or podosomal adhesion sites of monocyte-derived macrophages. Nogo-B positive structures are partially co-localized with RhoA staining and Rac1 positive membrane ruffles. Furthermore, Nogo-B is associated with the tubulin network, but not accumulated in the Golgi region. Although Nogo-B is present in the endoplasmic reticulum, it can also be translocated to large cell protrusions or the trailing end of migratory cells, where it is homogenously distributed.ConclusionsTwo different Nogo-B staining patterns can be distinguished in macrophages: firstly we observed ER-independent Nogo-B localization in cell protrusions and at the trailing end of migrating cells. Secondly, the localization of Nogo-B in actin/RhoA/Rac1 positive regions supports an influence on cytoskeletal organization. To our knowledge this is the first report on Nogo-B expression at the base of filopodia, thus providing further insight into the distribution of this protein.

Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition

“…This knowledge is important because different RTN3 variants might have specific biological functions in specific tissues or cells. Consistent with this concept, RTN4-B and RTN4-C variants appear to play specific roles in different tissues (Acevedo et al, 2004;Schanda et al, 2011;Tashiro et al, 2013). We have shown that RTN3 (also called RTN3-A1), similar to its binding partner BACE1, is strongly expressed in brain, mainly in various types of neurons, and is sparsely detected in resting astrocytes or microglia.…”

Nogo-B Facilitates LPS-Mediated Immune Responses by Up-Regulation of TLR4-Signaling in Macrophage RAW264.7

“…Marin et al have demonstrated a dramatic delay in the recruitment of macrophages in Nogo-B-disrupted mice in vivo , consistent with the findings of Schanda et al that Nogo-B deficiency is associated with reduced promotion of macrophage homing and functional recovery [17, 19]. Thus, it has been suggested that endogenous Nogo-B may be implicated in the control of macrophage activities and trafficking [20].…”

“…Recently, studies on Nogo-B have focused on its general role in regulating macrophage responses, including increasing chemokine-mediated monocyte/macrophage migration and infiltration, reducing the extent of ischemic injuries, and promoting wound healing [17, 18]. Marin et al have demonstrated a dramatic delay in the recruitment of macrophages in Nogo-B-disrupted mice in vivo , consistent with the findings of Schanda et al that Nogo-B deficiency is associated with reduced promotion of macrophage homing and functional recovery [17, 19].…”

NOGO-A/RTN4A and NOGO-B/RTN4B are simultaneously expressed in epithelial, fibroblast and neuronal cells and maintain ER morphology

“…Most of the data concerning the localization of RTN4 isoforms on ER membranes are based on over expression data4202122 although few studies have been done using antibodies against endogenous proteins232425. In our study, we used cell lines with different ER morphology and network organization to analyse the localization of endogenous NOGO-B/RTN4B and NOGO-A/RTN4A.…”