Leep2A and Leep2B function as a RasGAP complex to regulate macropinosome formation.

Macropinocytosis mediates the non-selective bulk uptake of extracellular fluid, enabling cells to survey the environment and obtain nutrients. A conserved set of signaling proteins orchestrates the actin dynamics that lead to membrane ruffling and macropinosome formation across various eukaryotic organisms. At the center of this signaling network are Ras GTPases, whose activation potently stimulates macropinocytosis. However, how Ras signaling is initiated and spatiotemporally regulated during macropinocytosis is not well understood. By using the model system Dictyostelium and a proteomics-based approach to identify regulators of macropinocytosis, we uncovered Leep2, consisting of Leep2A and Leep2B, as a RasGAP complex. The Leep2 complex specifically localizes to emerging macropinocytic cups and nascent macropinosomes, where it modulates macropinosome formation by regulating the activities of three Ras family small GTPases. Deletion or overexpression of the complex, as well as disruption or sustained activation of the target Ras GTPases, impairs macropinocytic activity. Our data reveal the critical role of fine-tuning Ras activity in directing macropinosome formation.

A transcription factor complex in Dictyostelium enables adaptive changes in macropinocytosis during the growth-to-development transition.

Macropinocytosis, an evolutionarily conserved endocytic pathway, mediates nonselective bulk uptake of extracellular fluid. It is the primary route for axenic Dictyostelium cells to obtain nutrients and has also emerged as a nutrient-scavenging pathway for mammalian cells. How cells adjust macropinocytic activity in various physiological or developmental contexts remains to be elucidated. We discovered that, in Dictyostelium cells, the transcription factors Hbx5 and MybG form a functional complex in the nucleus to maintain macropinocytic activity during the growth stage. In contrast, during starvation-induced multicellular development, the transcription factor complex undergoes nucleocytoplasmic shuttling in response to oscillatory cyclic adenosine 3',5'-monophosphate (cAMP) signals, which leads to increased cytoplasmic retention of the complex and progressive downregulation of macropinocytosis. Therefore, by coupling macropinocytosis-related gene expression to the cAMP oscillation system, which facilitates long-range cell-cell communication, the dynamic translocation of the Hbx5-MybG complex orchestrates a population-level adjustment of macropinocytic activity to adapt to changing environmental conditions.

A new form of Elongatoolithidae, Undulatoolithus pengi oogen. et oosp. nov. from Pingxiang, Jiangxi, China.

A new oogenus and oospecies of the Elongatoolithidae, Undulatoolithus pengi oogen. et oosp. nov., is described on the basis of specimens from the Upper Cretaceous Zhoutian Formation of the Pingxiang Basin, Jiangxi Province, China. The eggs are slightly asymmetrical, paired, and lay radially-oriented in a circular configuration within the clutch, and most suggestive of Macroolithus of the Elongatoolithidae by medium-sized eggs with average polar axis and equatorial diameter of 19.36 and 8.35 cm, and the ornamentation pattern of nodes and ridges on the outer surface. The new oogenus differs from Macroolithus in its prominent ridges 0.67 mm in height, about half of the entire eggshell thickness, gradational boundary between the cone layer and the overlying columnar layer, cone layer-to-columnar layer thickness ratio of 1/8 or 1/4. This discovery adds new data on the morphology and diversification of Late Cretaceous elongatoolithid ootaxa.