👤 Nicole Topp

A small fraction of the proteins present in human plasma can be found as circulating protein aggregates. Such aggregates are formed by prone to aggregation proteins and different stimuli promote the aggregation process. Fe(III) is a redox active metal ion which also actively interacts with proteins. The aim of this work is to identify the prone to aggregation plasma proteins in presence of Fe(III) in order to outline potential targets of these circulating protein aggregates. Here we show that Fe(III) induces the formation of protein aggregates from human plasma proteins. A concentration of 100 μM Fe(III) aggregates roughly 5 % of the total plasma protein assayed. When assayed by SDS-PAGE/silver-staining, a rather homogeneous aggregate can be observed with one major protein with a molecular weight matching that of immunoglobulin G (IgG) (150k Da). Additionally, the band corresponding to albumin (66 kDa) which is the main plasma protein was absent. The identity of IgG within the aggregate and albumin depletion was corroborated by liquid chromatography-mass spectrometry. Additionally, some other proteins could be identified within the aggregate such as fibrinogen, fibronectin and Apo-B. Then, the identity of the IgG and depletion of albumin was corroborated by Western blot. It should be noted that aggregated IgGs are strong activators of inflammatory pathways involving neutrophil oxidative burst, complement cascade activation and platelet release of active amines. Therefore, the existence of a potential link between the formation of Fe(III)-induced protein aggregates and inflammation should be further explored. Show less

The actin-based motor myosin-19 (Myo19) exerts force on mitochondrial membrane receptors Miro1/2, influencing endoplasmic reticulum (ER)-mitochondria contact sites and mitochondrial cristae structure. The mitochondrial intermembrane bridging (MIB) complex connects the outer and inner mitochondrial membranes at the cristae junction through the mitochondrial contact site and cristae organization system (MICOS). However, the interaction between Myo19, Miro1 and Miro2 (hereafter Miro1/2), and the MIB-MICOS complex in cristae regulation remains unclear. This study investigates the roles of Miro1/2 and metaxin 3 (Mtx3), a MIB complex component, in linking Myo19 to MIB-MICOS. We show that Miro1/2 interact with Myo19 and the MIB complex but not with Mtx3. Their mitochondrial membrane anchors are not essential for MIB interaction or cristae structure. However, Mtx3 is crucial for the connection between MIB-MICOS and the Myo19 and Miro1/2 proteins. Deleting Miro1/2 mimics the effects of Myo19 deficiency on ER-mitochondria contacts and cristae structure, whereas Mtx3 deletion does not. Notably, the loss of Myo19 and Miro1/2 alters mitochondrial lipid composition, reducing cardiolipin and its precursors, suggesting Myo19 and Miro1/2 influence cristae indirectly via lipid transfer at ER-mitochondria contact sites. Show less

The zebrafish adult brain contains numerous neural progenitors and is a good model to approach the general mechanisms of adult neural stem cell maintenance and neurogenesis. Here we use this model to test for a correlation between Fgf signaling and cell proliferation in adult progenitor zones. We report expression of Fgf signals (fgf3,4,8a,8b,17b), receptors (fgfr1-4), and targets (erm, pea3, dusp6, spry1,2,4, and P-ERK) and document that genes of the embryonic fgf8 synexpression group acquire strikingly divergent patterns in the adult brain. We further document the specific expression of fgf3, fgfr1-3, dusp6, and P-ERK in ventricular zones, which contain neural progenitors. In these locations, however, a comparison at the single-cell level of fgfr/P-ERK expression with bromo-deoxy-uridine (BrdU) incorporation and the proliferation marker MCM5 indicates that Fgf signaling is not specifically associated with proliferating progenitors. Rather, it correlates with the ventricular radial glia state, some of which only are progenitors. Together these results stress the importance of Fgf signaling in the adult brain and establish the basis to study its function in zebrafish, in particular in relation to adult neurogenesis. Show less