Translocation into the endoplasmic reticulum (ER) is an initial and crucial biogenesis step for all secreted and endomembrane proteins in eukaryotes. ER insertion can take place through the well-characterized signal recognition particle (SRP)-dependent pathway or the less-studied route of SRP-independent translocation. To better understand the prevalence of the SRP-independent pathway, we systematically defined the translocational dependence of the yeast secretome. By combining hydropathy-based analysis and microscopy, we uncovered that a previously unappreciated fraction of the yeast secretome translocates without the aid of the SRP. Furthermore, we validated a family of SRP-independent substrates-the glycosylphosphatidylinositol (GPI)-anchored proteins. Studying this family, we identified a determinant for ER targeting and uncovered a network of cytosolic proteins that facilitate SRP-independent targeting and translocation. These findings highlight the underappreciated complexity of SRP-independent translocation, which enables this pathway to efficiently cope with its extensive substrate flux.
Department of Biochemistry, College of Medicine, Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea. Electronic address:
Particulate matter 2.5 (PM) exposure is responsible for skin inflammation, aging, and disruption of skin homeostasis. The objective of this investigation was to assess the potential of myricetin in protecting against skin damage caused by PM.
Plants can experience a lack of oxygen due to environmental conditions such as flooding events or intense microbial blooms in the soil, and from their own metabolic activities. The associated limit on aerobic respiration can be fatal. Therefore, plants have evolved sensing systems that monitor oxygen levels and trigger a suite of metabolic, physiological and developmental responses to endure, or potentially escape, these oxygen limiting conditions.
Cytosolic thiouridylase is a conserved cytoplasmic tRNA thiolase composed of two different subunits, CTU1 and CTU2. CTU2 serves as a scaffold protein, while CTU1 catalyzes the 2-thiolation at the 34th wobble uridine of the anticodon loop. tRNAGlnUUG, tRNAGluUUC, and tRNALysUUU are the tRNA substrates that are modified with a thiol group at the C2 positions (s2) by CTU1, and also with a methoxycarbonylmethyl group at the C5 positions (mcm5) by Elongator and ALKBH8.
Water exists in the beginning and hydrates all matter. Life emerged in water, requiring three essential components in compartmentalized spaces: (1) universal energy sources driving biochemical reactions and processes, (2) molecules that store, encode, and transmit information, and (3) functional players carrying out biological activities and structural organization. Phosphorus has been selected to create adenosine triphosphate (ATP) as the universal energy currency, nucleic acids for genetic information storage and transmission, and phospholipids for cellular compartmentalization.
Glioblastoma cells rely on connexin 43 (Cx43)-based gap junctions (GJs) for intercellular communication, enabling them to integrate into a widely branched malignant network. Although there are promising prospects for new targeted therapies, the lack of clinically feasible GJ inhibitors has impeded their adoption in clinical practice. In the present study, we investigated tonabersat (TO), a blood-brain-barrier-penetrating drug with GJ-inhibitory properties, in regard to its potential to disassemble intercellular connectivity in glioblastoma networks.
