Neuroplastin splice variants Np55 and Np65: Who is doing the job in macrophages?

Neuroplastin, a paralog of CD147/Basigin, is known as a neuronal cell adhesion molecule and as an auxiliary subunit of plasma membrane calcium ATPases in both neurons and adaptive immune cells. Recently, an interesting study by Ren et al. (2022) provided evidence for an important role of neuroplastin in macrophages during bacterial infection.

Ca Homeostasis by Plasma Membrane Ca ATPase (PMCA) 1 Is Essential for the Development of DP Thymocytes.

The strength of Ca signaling is a hallmark of T cell activation, yet the role of Ca homeostasis in developing T cells before expressing a mature T cell receptor is poorly understood. We aimed to unveil specific functions of the two plasma membrane Ca ATPases expressed in T cells, PMCA1 and PMCA4. On a transcriptional and protein level we found that PMCA4 was expressed at low levels in CD4CD8 double negative (DN) thymocytes and was even downregulated in subsequent stages while PMCA1 was present throughout development and upregulated in CD4CD8 double positive (DP) thymocytes.

Plasma membrane Ca ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca homeostasis in mice.

The amplitude and duration of Ca signaling is crucial for B-cell development and self-tolerance; however, the mechanisms for terminating Ca signals in B cells have not been determined. In lymphocytes, plasma membrane Ca ATPase (PMCA) isoforms 1 and 4 (PMCA1 and PMCA4, aka ATP2B1 and ATP2B4) are the main candidates for expelling Ca from the cell through the plasma membrane. We report here that Pmca4 (Atp2b4) KO mice had normal B-cell development, while mice with a conditional KO of Pmca1 (Atp2b1) had greatly reduced numbers of B cells, particularly splenic follicular B cells, marginal zone B cells, and peritoneal B-1a cells.

A complex of Neuroplastin and Plasma Membrane Ca ATPase controls T cell activation.

The outcome of T cell activation is determined by mechanisms that balance Ca influx and clearance. Here we report that murine CD4 T cells lacking Neuroplastin (Nptn ), an immunoglobulin superfamily protein, display elevated cytosolic Ca and impaired post-stimulation Ca clearance, along with increased nuclear levels of NFAT transcription factor and enhanced T cell receptor-induced cytokine production. On the molecular level, we identified plasma membrane Ca ATPases (PMCAs) as the main interaction partners of Neuroplastin.

Constitutive and functional expression of YB-1 in microglial cells.

Y-box-binding protein (YB-1) is a member of the cold-shock protein family and participates in a wide variety of DNA/RNA-dependent cellular processes including DNA repair, transcription, mRNA splicing, packaging, and translation. At the cellular level, YB-1 is involved in cell proliferation and differentiation, stress responses, and malignant cell transformation. A general role for YB-1 during inflammation has also been well described; however, there are minimal data concerning YB-1 expression in microglia, which are the immune cells of the brain.