Stress-dependent proteolytic processing of the actin assembly protein Lsb1 modulates a yeast prion.

[wiskott-aldrich syndrome]

Yeast prions are self-propagating amyloid-like aggregates of Q /N-rich protein that confer heritable traits and provide a model of mammalian amyloidoses . [PSI (+)] is a prion isoform of the translation termination factor Sup 35 . Propagation of [PSI (+)] during cell division under normal conditions and during the recovery from damaging environmental stress depends on cellular chaperones and is influenced by ubiquitin proteolysis and the actin cytoskeleton . The paralogous yeast proteins Lsb 1 and Lsb 2 bind the actin assembly protein Las 17 (a yeast homolog of human Wiskott-Aldrich syndrome protein ) and participate in the endocytic pathway . Lsb 2 was shown to modulate maintenance of [PSI (+)] during and after heat shock . Here , we demonstrate that Lsb 1 also regulates maintenance of the Sup 35 prion during and after heat shock . These data point to the involvement of Lsb proteins in the partitioning of protein aggregates in stressed cells . Lsb 1 abundance and cycling between actin patches , endoplasmic reticulum , and cytosol is regulated by the Guided Entry of Tail-anchored proteins pathway and Rsp 5 -dependent ubiquitination . Heat shock-induced proteolytic processing of Lsb 1 is crucial for prion maintenance during stress . Our findings identify Lsb 1 as another component of a tightly regulated pathway controlling protein aggregation in changing environments .

Diseases
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Diseases presenting "self-propagating amyloid-like aggregates" symptom

wiskott-aldrich syndrome

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