• Issue

    FEBS Letters: Volume 596, Issue 22

    2853-2985
    November 2022

Issue Information

Free Access

Front Cover

  • Pages: 2853-2854
  • First Published: 27 November 2022
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Cover illustration Loss of GPHR induces neurodegeneration accompanied by Golgi fragmentation. The cover image refers to Sou et al. ‘GPHR-mediated acidification of the Golgi lumen is essential for cholesterol biosynthesis in the brain’.

The Scientists' Forum

Neuroscience

Free Access

Academic bullying and diversity: challenges and solutions

  • Pages: 2855-2858
  • First Published: 05 October 2022
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The promise of tenure is a driving force in higher education. Tenured faculty ultimately decide who receives the honor. The professoriate is disproportionally composed of white males and several factors, including unconscious bias, conspire to keep it that way. (Illustration created by Anna Peris, Lehigh Univeristy)

Review

Membrane trafficking, vesicles, organelle

Open Access

Disulfide bond formation and redox regulation in the Golgi apparatus

  • Pages: 2859-2872
  • First Published: 10 October 2022
Description unavailable

Catalyzed disulfide bond formation in the Golgi apparatus is more limited than in the endoplasmic reticulum and appears to have a regulatory function. The Golgi disulfide catalyst QSOX1 oxidizes glycosyltransferases and thereby influences sialic acid addition to glycans. QSOX1 is not required for the major disulfide-mediated protein complex assembly processes that occur in the Golgi.

Research Letters

Editor's Choice

Free Access

GPHR-mediated acidification of the Golgi lumen is essential for cholesterol biosynthesis in the brain

  • Pages: 2873-2888
  • First Published: 03 September 2022
Description unavailable

The Golgi pH regulator (GPHR) is essential for maintaining the integrity of the Golgi apparatus through the regulation of luminal acidic pH. We show here that loss of GPHR induced neurodegeneration accompanied by Golgi fragmentation. We also provide evidence that the Golgi luminal pH is indispensable for maintaining cholesterol levels via activation of the sterol regulatory element-binding protein SREBP2.

Neuroscience

Free Access

Astrocytic d-amino acid oxidase degrades d-serine in the hindbrain

  • Pages: 2889-2897
  • First Published: 03 June 2022
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d-Serine is a neuromodulator that binds to N-methyl-d-aspartate glutamate receptors and is regulated by d-amino acid oxidase (DAO). Conditional knockout of DAO in glial fibrillary acidic protein-positive astrocytes reveals that astrocytic DAO degrades d-serine specifically in the hindbrain, but not in the forebrain nor in the peripheral organs. This study enhances understanding of neuromodulation by d-serine and provides a tool to study DAO-associated neuronal diseases.

Research Articles

Protein homeostasis

Free Access

The ubiquitin–proteasome system and autophagy mutually interact in neurotoxin-induced dopaminergic cell death models of Parkinson's disease

  • Pages: 2898-2913
  • First Published: 24 August 2022
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We investigated the dynamic interplay between the ubiquitin–proteasome system (UPS) and the autophagy–lysosomal pathway (ALP) in two neurotoxin-induced cell death models of Parkinson's disease. In dopaminergic MN9D cells, treatment with the neurotoxin 6-OHDA caused excessive autophagy, whereas treatment with the neurotoxin MPP+ impaired autophagy. Both toxins inhibited proteasome activity. Furthermore, UPS or ALP inhibition differentially modulated their activities during neurotoxin-induced cell death. Our results indicate that crosstalk between UPS and ALP affects neuronal cell death.

Neuroscience

Open Access

cAMP-induced decrease in cell-surface laminin receptor and cellular prion protein attenuates amyloid-β uptake and amyloid-β-induced neuronal cell death

  • Pages: 2914-2927
  • First Published: 06 August 2022
Description unavailable

We find that in Neuroscreen-1 neuronal cells, 67 kDa laminin receptor (67LR) is the major co-receptor for cellular prion protein (PrPC)-mediated uptake of amyloid-β oligomers (AβO) and neuronal cell death. Both pharmacological and physiological cAMP-elevating agents acting via protein kinase A pathway decrease cell-surface levels of 67LR and PrPC and thereby decrease uptake of AβO and neuronal cell death.

Research Letters

Biophysics

Open Access

Heparin promotes rapid fibrillation of the basic parathyroid hormone at physiological pH

  • Pages: 2928-2939
  • First Published: 28 July 2022
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At low physiological pH, the parathyroid hormone is a positively charged peptide that remains in a soluble monomeric state over time. We show in vitro that high affinity binding to the polyanion heparin leads to higher-order assemblies and, finally, PTH fibrillation. We propose that PTH conversion into functional amyloid fibrils might rely on similar polyanionic structures in vivo.

Metabolism

Free Access

STAT3 transcriptionally regulates the expression of genes related to glycogen metabolism in developing motor neurons

  • Pages: 2940-2951
  • First Published: 01 September 2022
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In this study, we identified cis-regulatory elements in the mouse genome that regulate the expression of glycogen synthase1 (Gys1) and glycogen phosphorylase brain form (PygB) in the developing spinal cord. We found that STAT3 transcriptionally induced expression of both Gys1 and PygB in the developing spinal cord, suggesting the importance of STAT3 in the regulation of glycogen metabolism.

Research Article

Neuroscience

Free Access

Myelin-associated glycoprotein alters the neuronal secretome and stimulates the release of TGFβ and proteins that affect neural plasticity

  • Pages: 2952-2973
  • First Published: 14 September 2022
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In this study, we show that soluble forms of myelin-associated glycoprotein (MAG) and Nogo induce secretion of transforming growth factor β in neurons. MAG also has broad effects on the neuronal secretome, promoting secretion of proteins that negatively affect neuronal survival, while inhibiting the secretion of factors that promote axonal growth and synaptogenesis.

Research Letter

Neuroscience

Free Access

Calmodulin promotes a Ca2+-dependent conformational change in the C-terminal regulatory domain of CaV1.2

  • Pages: 2974-2985
  • First Published: 30 October 2022
Description unavailable

Here, we report binding of calmodulin (CaM) to the C-terminal domain of CaV1.2 (CT(1520–1669)) to probe conformational changes that regulate channel function. The refolding of CT(1520–1669) in the presence of Ca2+-saturated CaM forms a soluble complex. The same refolding in the presence of apoCaM does not form a complex, consistent with a lack of apoCaM binding to CaV1.2.