Researchers discover how cells modulate macropinocytic activity

Macropanocytosis is one of the major pathways by which cells nonselectively internalize extracellular fluids. The laboratory strain Dictyostelium discoideum serves as a valuable model to study the regulation of macropinocytosis.

This model cell is a social amoeba that exists as a A single cell When nutrients are abundant and use macropinocytosis to acquire nutrients. Under conditions of nutritional deficiency, it enters a Stages of development and undergoes directed migration to form multicellular structures. gave Molecular mechanisms The reason behind this transition from macropinocytosis to transition mode is still unclear.

In one study published I Developmental cells On February 6, researchers led by Professor Kai Huaqing of the Institute of Biophysics of the Chinese Academy of Sciences, together with Professor Li Li of Peking University, revealed the molecular mechanisms by which cells undergo macropinocytosis in response to nutrients. regulate the level of Stress

Further through genetic screening and Mass spectrometryresearchers first identified two transcription factors, Hbx5 and MybG, that are involved in macropinocytosis.

Using microscopy, biochemical experiments, RNA-Seq, and ChIP-Seq, the researchers found that Hbx5 and MybG form a heterodimeric complex. During the nutritive growth phase, this complex forms locally. The cell nucleus and regulates the expression of genes involved in macropinocytosis, maintaining high levels of macropinocytosis.

Under nutritional stress, oscillatory cAMP signaling causes the Hbx5-MybG complex to undergo nucleocytoplasmic shuttling, resulting in the downregulation of genes involved in macropinocytosis. As the frequency of cAMP oscillatory signaling increases during development, the Hbx5-MybG complex ceases shuttling and becomes trapped in the cytoplasm, turning off the expression of genes promoting macropinocytosis and directed migratory behavior. Makes the transition easier.

This study has identified key regulatory components that enable cells to maintain macropinocytosis and alter its levels in response to nutritional stress. This not only provides new insights into the molecular mechanisms by which cells control macropinocytosis. Environmental changes It also opens new avenues to study the mechanisms of oscillatory signaling in cells.