Glucocorticoid receptors function in the pathophysiology of brain hypoxia

Glucocorticoid receptors are ligand-activated transcription factors, which play an important role in the brain, mainly in stress response regulation. There are two types of receptors for glucocorticosteroids: mineralocorticoid receptors (MR) with high-affinity for the ligands and glucocorticoid receptors (GR) with a tenfold lower affinity. Selective activation of the receptors during hypoxia may decide neuronal fate, especially in the hippocampus. Depending on the severity of hypoxia-induced damage, neurons undergo necrosis or apoptosis. In the penumbral region, where neurons die mainly through the process of apoptosis, selective GR activation increases excitotoxicity, interferes with apoptotic signalling pathways and causes energy deficit in the cells, all of which promote cell death. On the other hand, selective MR activation seems to be neuroprotective. It is suggested that the main role of MR in neuroprotection is to regulate the balance between anti- and proapoptotic proteins from bcl-2 family

Glucocorticoid receptors function in the pathophysiology of brain hypoxia

Glucocorticoid receptors are ligand-activated transcription factors, which play an important role in the brain, mainly in stress response regulation. There are two types of receptors for glucocorticosteroids: mineralocorticoid receptors (MR) with high-affinity for the ligands and glucocorticoid receptors (GR) with a tenfold lower affinity. Selective activation of the receptors during hypoxia may decide neuronal fate, especially in the hippocampus. Depending on the severity of hypoxia-induced damage, neurons undergo necrosis or apoptosis. In the penumbral region, where neurons die mainly through the process of apoptosis, selective GR activation increases excitotoxicity, interferes with apoptotic signalling pathways and causes energy deficit in the cells, all of which promote cell death. On the other hand, selective MR activation seems to be neuroprotective. It is suggested that the main role of MR in neuroprotection is to regulate the balance between anti- and proapoptotic proteins from bcl-2 family

Gγ and Gα Identity Dictate a G-Protein Heterotrimer Plasma Membrane Targeting

Heterotrimeric G-proteins along with G-protein-coupled receptors (GPCRs) regulate many biochemical functions by relaying the information from the plasma membrane to the inside of the cell. The lipid modifications of Gα and Gγ subunits, together with the charged regions on the membrane interaction surface, provide a peculiar pattern for various heterotrimeric complexes. In a previous study, we found that Gαs and Gαi3 prefer different types of membrane-anchor and subclass-specific lipid domains. In the present report, we examine the role of distinct Gγ subunits in the membrane localization and spatiotemporal dynamics of Gαs and Gαi3 heterotrimers. We characterized lateral diffusion and G-protein subunit interactions in living cells using fluorescence recovery after photobleaching (FRAP) microscopy and fluorescence resonance energy transfer (FRET) detected by fluorescence lifetime imaging microscopy (FLIM), respectively. The interaction of Gγ subunits with specific lipids was confirmed, and thus the modulation of heterotrimeric G-protein localization. However, the Gα subunit also modulates trimer localization, and so the membrane distribution of heterotrimeric G-proteins is not dependent on Gγ only

G\gamma and G\alpha identity dictate a G-protein heterotrimer plasma membrane targeting

Heterotrimeric G-proteins along with G-protein-coupled receptors (GPCRs) regulate many biochemical functions by relaying the information from the plasma membrane to the inside of the cell. The lipid modifications of Gα and Gγ subunits, together with the charged regions on the membrane interaction surface, provide a peculiar pattern for various heterotrimeric complexes. In a previous study, we found that Gαs and Gαi3 prefer different types of membrane-anchor and subclass-specific lipid domains. In the present report, we examine the role of distinct Gγ subunits in the membrane localization and spatiotemporal dynamics of Gαs and Gαi3 heterotrimers. We characterized lateral diffusion and G-protein subunit interactions in living cells using fluorescence recovery after photobleaching (FRAP) microscopy and fluorescence resonance energy transfer (FRET) detected by fluorescence lifetime imaging microscopy (FLIM), respectively. The interaction of Gγ subunits with specific lipids was confirmed, and thus the modulation of heterotrimeric G-protein localization. However, the Gα subunit also modulates trimer localization, and so the membrane distribution of heterotrimeric G-proteins is not dependent on Gγ only

Reconstitution of morphogen shuttling circuits

Here we provide raw data, code, and other supplementary material related to the manuscript, "Reconstitution of morphogen shuttling circuits," by Ronghui Zhu et al. This includes computer codes for implementing the shuttling model, maps of constructs used in this manuscript, raw imaging and flow cytometry data, and raw time-lapse images

[Revision] Reconstitution of morphogen shuttling circuits

Here we provide raw data, code, and other supplementary material related to the manuscript, "Reconstitution of morphogen shuttling circuits," by Ronghui Zhu et al. This includes computer codes for implementing the shuttling model, maps of constructs used in this manuscript, raw imaging and flow cytometry data, and raw time-lapse images.&nbsp