The Ca2+ Sensor Protein Swiprosin-1/EFhd2 Is Present in Neurites and Involved in Kinesin-Mediated Transport in Neurons

Abstract

Swiprosin-1/EFhd2 (EFhd2) is a cytoskeletal Ca2+ sensor protein strongly expressed in the brain. It has been shown to interact with mutant tau, which can promote neurodegeneration, but nothing is known about the physiological function of EFhd2 in the nervous system. To elucidate this question, we analyzed EFhd2−/−/lacZ reporter mice and showed that lacZ was strongly expressed in the cortex, the dentate gyrus, the CA1 and CA2 regions of the hippocampus, the thalamus, and the olfactory bulb. Immunohistochemistry and western blotting confirmed this pattern and revealed expression of EFhd2 during neuronal maturation. In cortical neurons, EFhd2 was detected in neurites marked by MAP2 and co-localized with pre- and post-synaptic markers. Approximately one third of EFhd2 associated with a biochemically isolated synaptosome preparation. There, EFhd2 was mostly confined to the cytosolic and plasma membrane fractions. Both synaptic endocytosis and exocytosis in primary hippocampal EFhd2−/− neurons were unaltered but transport of synaptophysin-GFP containing vesicles was enhanced in EFhd2−/− primary hippocampal neurons, and notably, EFhd2 inhibited kinesin mediated microtubule gliding. Therefore, we found that EFhd2 is a neuronal protein that interferes with kinesin-mediated transport.

Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy

“…Previous studies [17, 20, 21] showed that swiprosin-1 was widely accumulated in tissues such as the spleen, lung, liver, heart, and brain in particular. Swiprosin-1 was also expressed in immune cells such as human and primary murine mast cells [14], murine B cells, T cells [15-17], macrophages, natural killer cells [18, 19], and human peripheral blood mononuclear cells [20].…”

“…Swiprosin-1 was also expressed in immune cells such as human and primary murine mast cells [14], murine B cells, T cells [15-17], macrophages, natural killer cells [18, 19], and human peripheral blood mononuclear cells [20]. Protein atlas database indicates that swiprosin-1 is moderately expressed in human renal glomeruli but not tubules (http://www.proteinatlas.org/ENSG00000142634-$EFHD2/tissue/kidney#imid_13574299), which is consistent with the finidng of the present study that swiprosin-1 was moderately expressed in podocytes of renal glomeruli.…”

“…Swiprosin-1, also known as EF hand domain containing 2 (EFhd2), was initially identified as a novel protein in human CD8 + lymphocytes [14], and subsequently in immature, resting or activated B cells [15-17], macrophages and natural killer cells [18, 19], and non-lymphoid tissues such as the brain, spleen, lung, liver and heart [17, 20, 21]. In murine B cells, ectopic expression of swiprosin-1 was found to enhance spontaneous and B-cell receptor induced apoptosis [16, 22].…”

“…In murine B cells, ectopic expression of swiprosin-1 was found to enhance spontaneous and B-cell receptor induced apoptosis [16, 22]. In addition, swiprosin-1 was found to be involved by signaling cascades involving Ca 2+ [19, 20], protein kinase C, and nuclear factor-κB [23]. Also, swiprosin-1 was reported to be involved in the process of caspase-9-protein complexes in non-small cell lung cancer (NSCLC) cells and may promote caspase-9 activation, which may be linked to cell apoptosis [24].…”

Swiprosin‐1: Its Expression and Diverse Biological Functions

“…On the other hand, in murine neurites, co‐localization of swiprosin‐1 with tau, MAP2, synapsin 1a/b, and PSD‐95 signifying that swiprosin‐1 could be also associated with transport vesicles delivering synaptic proteins and it serve as a synaptic protein. For example, swiprosin‐1 ‐/‐ mice increases the speed of axonal transport but its presence inhibited the KIF5A (kinesin) mediated MT (microtubules) gliding in a dose‐dependent manner [Purohit et al, ]. Similarly, Borger et al also showed knockdown of swiprosin‐1 facilitates the development of a larger number of synapses in neurons but did not affect their ability to convert to mature synapses by recruiting postsynaptic densities [Borger et al, ].…”