The fly brain lands in Tokyo: A report on the 3rd Asia Pacific Drosophila Neurobiology Conference.

The third Asia Pacific Drosophila Neurobiology Conference (APDNC3) was held in the Wako Campus of RIKEN in Tokyo, Japan, from February 27th to March 1st, 2024. While APDNC2 was held in Taiwan in 2019, the global coronavirus pandemic enforced a long hiatus. Hence, APDNC3 was a much-anticipated meeting that attracted ~218 scientists from 18 different countries and regions, 154 from outside Japan.

Activation of PDGFRA signaling contributes to filamin C-related arrhythmogenic cardiomyopathy.

truncating mutations () are prevalent causes of inherited dilated cardiomyopathy (DCM), with a high risk of developing arrhythmogenic cardiomyopathy. We investigated the molecular mechanisms of mutant FLNC in the pathogenesis of arrhythmogenic DCM (a-DCM) using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). We demonstrated that iPSC-CMs from two patients with different mutations displayed arrhythmias and impaired contraction.

Up-regulation of voltage-gated sodium channels by peptides mimicking S4-S5 linkers reveals a variation of the ligand-receptor mechanism.

Prokaryotic Na channels are tetramers and eukaryotic Na channels consist of a single subunit containing four domains. Each monomer/domain contains six transmembrane segments (S1-S6), S1-S4 being the voltage-sensor domain and S5-S6 the pore domain. A crystal structure of NaMs, a prokaryotic Na channel, suggests that the S4-S5 linker (S4-S5) interacts with the C-terminus of S6 (S6) to stabilize the gate in the open state.

Voltage-dependent activation in EAG channels follows a ligand-receptor rather than a mechanical-lever mechanism.

Ether-a-go-go family (EAG) channels play a major role in many physiological processes in humans, including cardiac repolarization and cell proliferation. Cryo-EM structures of two of them, K10.1 and human ether-a-go-go-related gene (hERG or K11.

Building Atomic Models of the Ion Channels Based on Low Resolution Electron Microscopy Maps and Homology Modeling.

Voltage-gated potassium channels play pivotal roles in excitable and non-excitable cells. For many decades, structural properties and molecular mechanisms of these channels were inferred from functional observations. At the turn of the twenty-first century, structural biology revealed major aspects in the structural basis of ion channel organization, permeation, and gating.

Phosphatidylinositol (4,5)-bisphosphate-mediated pathophysiological effect of HIV-1 Tat protein.

Human immunodeficiency virus (HIV)-infected cells actively release the transcriptional activator (Tat) viral protein that is required for efficient HIV gene transcription. Extracellular Tat is able to enter uninfected cells. We recently reported that internalized Tat escapes endosomes to reach the cytosol and is then recruited to the plasma membrane by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P).

hERG S4-S5 linker acts as a voltage-dependent ligand that binds to the activation gate and locks it in a closed state.

Delayed-rectifier potassium channels (hERG and KCNQ1) play a major role in cardiac repolarization. These channels are formed by a tetrameric pore (S5-S6) surrounded by four voltage sensor domains (S1-S4). Coupling between voltage sensor domains and the pore activation gate is critical for channel voltage-dependence.

HIV-Tat induces a decrease in I and Ivia reduction in phosphatidylinositol-(4,5)-bisphosphate availability.

Patients with HIV present with a higher prevalence of QT prolongation, of which molecular bases are still not clear. Among HIV proteins, Tat serves as a transactivator that stimulates viral genes expression and is required for efficient HIV replication. Tat is actively secreted into the blood by infected T-cells and affects organs such as the heart.

Physiological and Pathophysiological Insights of Nav1.4 and Nav1.5 Comparison.

Mutations in Nav1.4 and Nav1.5 α-subunits have been associated with muscular and cardiac channelopathies, respectively.