Current research in cell biology最新文献

Proper control of mitochondrial morphology is crucial for many vital cellular processes including energy production, cell cycle and apoptosis. We show here that extracellular matrix (ECM) stiffness regulates mitochondrial morphology through integrin-dependent signaling pathways. ECM stiffening promotes mitochondrial fusion and concomitantly suppressed DRP1 expression and mitochondrial fission. Depletion of kindlin-2, an integrin-binding protein, inhibits ECM stiffening-induced mitochondrial fusion but fails to release ECM stiffening-induced suppression of DRP1 expression and mitochondrial fission. On the other hand, depletion of PINCH-1, a focal adhesion protein whose level is increased in response to ECM stiffening, does not significantly affect mitochondrial fusion but abolishes ECM stiffening-induced suppression of DRP1 expression and mitochondrial fission. Finally, overexpression of PINCH-1 is sufficient to override ECM softening-induced up-regulation of DRP1 expression and mitochondrial fission. Our results demonstrate a crucial role of ECM mechanics in regulation of mitochondrial dynamics and suggest that this regulation is mediated through two distinct signaling mechanisms, namely kindlin-2-dependent up-regulation of mitochondrial fusion and PINCH-1-dependent suppression of DRP1 expression and mitochondrial fission.

After completion of meiosis I, the oocyte immediately enters meiosis II and forms a metaphase II (MII) spindle without an interphase, which is fundamental for generating a haploid gamete. Here, we identify tudor domain-containing protein 3 (Tdrd3) as a novel regulator of oocyte meiosis. Although early mitotic inhibitor 2 (Emi2) protein has been shown to ensure the meiosis I to II transition and the subsequent MII spindle formation by inhibiting the anaphase-promoting complex/cyclosome (APC/C), how it accumulates after meiosis I has remained unresolved. We isolated Tdrd3 as a protein binding specifically and directly to Emi2 mRNA. In GV-stage mouse oocytes, Emi2 mRNA assembled into RNA granules containing Tdrd3, while cyclin B1 mRNA, which was translated in early meiosis I, formed different granules. Knockdown of Tdrd3 attenuated Emi2 synthesis in meiosis II without affecting cyclin B1 synthesis in meiosis I. Moreover, Tdrd3-deficient oocytes entered interphase and failed to form an MII spindle after completion of meiosis I. These defects were rescued by GFP-Emi2 expressed after meiosis I. Taken together, our results demonstrate the importance of Tdrd3-mediated translational control of Emi2 mRNA, which promotes Emi2 synthesis in meiosis II, for the progression of meiosis.

After colonization of the mosquito midgut by the malaria parasite, Plasmodium differentiates from an invasive, motile ookinete to a multiplicative, sessile oocyst. Despite their importance in establishing the infection and increasing its population, relatively little is known about the early morphological transformation associated with these changes in function. Oocyst differentiation begins with the formation of a spherical protrusion near the center of the crescent-shaped ookinete. As this protuberance grows, it engulfs the content of the two distal ends, thus rounding the cell. In this work, scrutinized observations of the overall changes in shape, coupled with the migration of the malaria pigment granules and the nucleus into the protuberance, revealed that the movement of the cell content happens in an anteroposterior manner. The resulting data, formalized as morphometric measurements, led to the identification of 5 transitional stages and to the development of a computer training algorithm that automatically classifies them. Since cell differentiation has been associated with redox fluctuations, the classification algorithm was tested with parasites stained with a glutathione-specific fluorescent probe. This revealed changes in the glutathione content during differentiation that are suggestive of a redox modulation during transformation.

Efficient contraction of the heart relies on a highly regulated communication network between cardiac cells. Direct intercellular communication is mediated by gap junctions but can also occur through tubular structures named tunnelling nanotubes (TNTs), which connect the cytoplasm of neighbouring cells and facilitate the transport of various cargoes. Although the formation of TNTs between cardiomyocytes has been reported, the effect of ischaemia on this process remains unclear. In this work, we assessed the impact of ischaemia and oxidative stress on TNT-mediated communication between cardiac cells. We found that cardiac cell lines and neonatal primary cultures of cardiomyocytes subjected to in vitro ischaemia form more TNTs than control cells. Moreover, antioxidants prevented ischaemia-induced TNT formation, suggesting that oxidative stress regulates this process. Furthermore, we identified troponin T as a new specific marker of cardiomyocyte-derived TNTs, which allows for the identification of heterocellular TNT connections between cardiomyocytes and other resident cells in the heart, such as fibroblasts. We also determined the presence of TNT-like structures in rat and human hearts. Rat hearts subjected to global ischaemia in the ex vivo Langendorff system showed increased formation of TNTs. Altogether, this study demonstrates that ischaemia affects the formation of TNTs in the heart and sheds new light on the regulation of TNT-mediated communication between cardiomyocytes.

Acute Respiratory Distress Syndrome is a severe disorder affecting thousands of individuals worldwide. The available medical countermeasures do not sufficiently suppress the unacceptable high mortality rates associated with those in need. Thus, intense efforts aim to delineate the function of the lung endothelium, so to deliver new therapeutic approaches against this disease. The present manuscript attempts to shed light on the interrelations between the unfolded protein response and autophagy towards lung disease, to deliver a new line of possible therapeutic approaches against the ferocious Acute Respiratory Distress Syndrome.