Biology subjects

Westermann, S.

Publications and source records attributed to Westermann, S..

2 recordsLinked to original sources

bioRxiv2021

Differentially accessible Cdc4 phospho-degrons regulate Ctf19CCAN kinetochore subunit stability in mitosis

Kinetochores are multi-subunit protein assemblies that link chromosomes to microtubules of the mitotic and meiotic spindle. How effective, yet strictly centromere-dependent kinetochore assembly is coupled to cell cycle progression is incompletely understood. Here, by combining comprehensive phosphorylation analysis of native Ctf19CCAN subunits with biochemical and functional assays in the model system budding yeast, we demonstrate that Cdk1 phosphorylation activates phospho-degrons on the essential subunit Ame1CENP-U which are recognized by the E3 ubiquitin ligase complex SCF-Cdc4. Gradual phosphorylation of degron motifs culminates in M-Phase and targets the protein for degradation. Binding of the Mtw1 complex shields the proximal phospho-degron, protecting kinetochore-bound Ame1 from the degradation machinery. Artificially increasing degron strength partially suppresses the temperature-sensitivity of a cdc4 mutant, while overexpression of Ame1-Okp1 is toxic to cells, demonstrating the physiological importance of this mechanism. We propose that phospho-regulated clearance of excess CCAN subunits protects against ectopic kinetochore assembly and contributes to mitotic checkpoint silencing. Our results suggest a novel strategy for how phospho-degrons can be used to regulate the assembly of multi-subunit complexes.

cell biology↗

bioRxiv2020

Selective REM-Sleep Suppression Increases Next-Day Negative Affect and Amygdala Responses to Social Exclusion

Healthy sleep, positive general affect, and the ability to regulate emotional experiences are fundamental for well-being. In contrast, various mental disorders are associated with altered rapid eye movement (REM) sleep, negative affect, and diminished emotion regulation abilities. However, the neural processes mediating the relationship between these different phenomena are still not fully understood. In the present study of 42 healthy volunteers, we investigated the effects of selective REM sleep suppression (REMS) on general affect, as well as on feelings of social exclusion, emotion regulation, and their neural underpinnings. Using functional magnetic resonance imaging we show that REMS increases amygdala responses to experimental social exclusion, as well as negative affect on the morning following sleep deprivation. There was no evidence that emotional responses to experimentally induced social exclusion or their regulation using cognitive reappraisal were impacted by diminished REM sleep. Our findings indicate that general affect and amygdala activity depend on REM sleep, while specific emotional experiences possibly rely on additional psychological processes and neural systems that are less readily influenced by REMS.

neuroscience↗