Biology subjects

Omnus, D. J.

Publications and source records attributed to Omnus, D. J..

4 recordsLinked to original sources

bioRxiv2022

The heat shock protein LarA activates the Lon protease at the onset of proteotoxic stress.

The Lon protease is a highly conserved protein degradation machine that has critical regulatory and protein quality control functions in cells from the three domains of life. Here, we report the discovery of a -proteobacterial heat shock protein, LarA, that functions as a dedicated Lon regulator. We show that LarA accumulates at the onset of proteotoxic stress and allosterically activates Lon-catalysed degradation of a large group of substrates through a five amino acid sequence at its C-terminus. Further, we find that LarA is regulated by Lon itself, which is critical to prevent toxic overactivation of Lon. We suggest that the temporal LarA-dependent activation of Lon helps to meet an increased proteolysis demand at the onset of protein unfolding stress. Our study defines a regulatory interaction of a conserved protease with a heat shock protein, serving as a paradigm of how protease activity can be tuned under changing environmental conditions.

molecular biology↗

bioRxiv2021

The Lon protease temporally restricts polar cell differentiation events during the Caulobacter cell cycle

The highly conserved protease Lon has important regulatory and protein quality control functions in cells from the three domains of life. Despite many years of research on Lon, only few specific protein substrates are known in most organisms. Here, we used a quantitative proteomics approach to identify novel substrates of Lon in the dimorphic bacterium Caulobacter crescentus. We focused our study on proteins involved in polar cell differentiation and investigated the developmental regulator StaR and the flagella hook length regulator FliK as specific Lon substrates in detail. We show that Lon recognizes these proteins at their C-termini, and that Lon-dependent degradation ensures their temporally restricted accumulation in the cell cycle phase when their function is needed. Disruption of this precise temporal regulation of StaR and FliK levels in a{Delta} lon mutant contributes to defects in stalk biogenesis and motility, respectively, revealing a critical role of Lon in coordinating developmental processes with cell cycle progression. Our work underscores the importance of Lon in the regulation of complex temporally controlled processes by adjusting the concentrations of critical regulatory proteins. Furthermore, this study includes the first characterization of FliK in C. crescentus and uncovers a dual role of the C-terminal amino acids of FliK in protein function and degradation.

microbiology↗

bioRxiv2021

Tricalbin proteins regulate plasma membrane phospholipid homeostasis

The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer proteins that function at contacts between the endoplasmic reticulum and plasma membrane (ER-PM contacts). However, roles of the E-Syt family members in PM lipid organisation remain unclear. Among the E-Syt family, the yeast tricalbin (Tcb) proteins are essential for PM integrity upon heat stress, but it is not known how they contribute to PM maintenance. Using quantitative lipidomics and microscopy, we find that the Tcb proteins regulate phosphatidylserine homeostasis at the PM. Moreover, upon heat-induced membrane stress, Tcb3 co-localises with the PM protein Sfk1 that is implicated in PM phospholipid asymmetry and integrity. The Tcb proteins also promote the recruitment of Pkh1, a stress-activated protein kinase required for PM integrity. Phosphatidylserine has evolutionarily conserved roles in PM organisation, integrity, and repair. We suggest that phospholipid regulation is an ancient essential function of E-Syt family members in PM integrity.

cell biology↗

bioRxiv2018

A Cytoplasmic GOLD Protein Controls Cell Polarity

Phosphoinositide lipids provide spatial landmarks during polarized secretion. Here, we elucidate a role for phosphatidylinositol 4-phosphate (PI4P) metabolism in the control of cell polarity. In budding yeast, PI4P is enriched at the plasma membrane of growing daughter cells. Upon heat shock however, PI4P rapidly increases at the plasma membrane in mother cells resulting in a more uniform PI4P distribution. Rather than phosphoinositide kinase activation, PI4P hydrolysis is impaired to generate the heat-induced PI4P signal in mother cells. This fine tune control of PI4P metabolism is mediated through attenuation of the Osh3 protein that binds and presents PI4P to a phosphoinositide phosphatase. Importantly, Osh3 undergoes phase transitions upon environmental stress conditions, resulting in intracellular aggregates and reduced cortical localization. The chaperone Hsp104 co-assembles with intracellular Osh3 granules, but is not required for their formation. Interestingly, the Osh3 GOLD domain, also present in the ER-localized p24 cargo adaptor family, is sufficient to form stress granules. Accordingly, GOLD-mediated phase transitions may provide a general mechanism to modulate secretion and growth upon transient changes in physiological and environmental conditions.

cell biology↗