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Biology subjects

Izawa, S.

Publications and source records attributed to Izawa, S..

2 recordsLinked to original sources

Thermosensitivity of cellular translation restricts the growth of fission yeast at high temperatures

Living organisms have thermal limits above which they are unable to operate and survive. Our previous genetic screen identified proteins that impede the high-temperature growth of fission yeast, including the RNA-binding protein Dri1 and a fission yeast-specific protein termed Rhs1. Here, we show that Dri1 and Rhs1 form a complex and physically interact with the Ccr4-Not complex, a master regulator of mRNA metabolism. Gene expression analysis revealed that the Dri1-Rhs1 and Ccr4-Not complexes negatively regulate a set of genes implicated in ribosome biogenesis (Ribi genes). Loss of the Dri1-Rhs1 complex results in the augmented expression of Ribi genes, thereby suppressing the accumulation of 80S monosomes and the growth inhibition under high-temperature conditions. The thermosensitivity of the translational processes may be a determinant of the upper limit of the growth temperature in fission yeast.

cell biology↗

Dissociating orexin-dependent and -independent functions of orexin neurons using novel orexin-Flp knock-in mice

Uninterrupted arousal is important for survival during threatening situations. Activation of orexin/hypocretin neurons is implicated in sustained arousal. However, orexin neurons produce and release orexin as well as several co-transmitters including dynorphin and glutamate. Thus, it is important to disambiguate orexin peptide-dependent and -independent physiological functions of orexin neurons. To attain this, we generated a novel orexin-flippase (Flp) knock-in (KI) mouse line. Crossing with Flp-reporter or Cre-expressing mice showed gene expression exclusively in orexin neurons. Histological studies confirmed that orexin was completely knock-out (KO) in KI/KI homozygous mice. Orexin neurons without orexin showed altered electrophysiological properties, as well as received decreased glutamatergic inputs. Selective chemogenetic activation revealed that both orexin and co-transmitters functioned to increase wakefulness, however, orexin was indispensable to promote sustained arousal. Surprisingly, activation of orexin neurons without orexin caused a significant increase in the total time spent in cataplexy. Taken together, orexin is essential to maintain basic membrane properties and input-output computation of orexin neurons, as well as to exert awake-sustaining aptitude of orexin neurons.

neuroscience↗