A5030968321- Cellular transport and secretion
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Bacterial Genetics and Biotechnology
- Physiological and biochemical adaptations
- Fungal and yeast genetics research
- Ubiquitin and proteasome pathways
- Vibrio bacteria research studies
- Bacterial biofilms and quorum sensing
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Lipid Membrane Structure and Behavior
- Enzyme Structure and Function
- Ion channel regulation and function
- Cancer Research and Treatments
- Antibiotic Resistance in Bacteria
- Enzyme Production and Characterization
- Protein Tyrosine Phosphatases
- RNA modifications and cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Genetics, Aging, and Longevity in Model Organisms
- DNA Repair Mechanisms
- Phytase and its Applications
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
Science for Life Laboratory
2018-2023
Stockholm University
2010-2023
MRC Laboratory for Molecular Cell Biology
2016-2022
University College London
2016-2022
Medical Research Council
2022
University of Freiburg
2021
Medizinische Hochschule Hannover
2011
Wenner-Gren Foundations
2010
Membrane lipid dynamics must be precisely regulated for normal cellular function, and disruptions in homeostasis are linked to the progression of several diseases. However, little is known about sensory mechanisms detecting membrane composition how metabolism response stress. We find that phosphoinositide (PI) kinase signaling controls a conserved PDK-TORC2-Akt cascade as part network allows endoplasmic reticulum (ER) modulate essential responses, including Ca 2+ -regulated biogenesis, upon...
The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer that function at contacts between the ER and plasma membrane (ER-PM contacts). However, roles of E-Syt family members in PM organisation remain incomplete. Among family, yeast tricalbin (Tcb) essential for integrity upon heat stress, but it is not known how they contribute to maintenance. Using quantitative lipidomics microscopy, we find Tcb regulate phosphatidylserine homeostasis PM....
The Lon protease is a highly conserved protein degradation machine that has critical regulatory and quality control functions in cells from the three domains of life. Here, we report discovery α-proteobacterial heat shock protein, LarA, as dedicated regulator. We show LarA accumulates at onset proteotoxic stress allosterically activates Lon-catalysed large group substrates through five amino acid sequence its C-terminus. Further, find high levels cause growth inhibition Lon-dependent manner...
Regulated proteolysis serves as a mechanism to control cellular processes. The SPS (Ssy1-Ptr3-Ssy5) sensor in yeast responds extracellular amino acids by endoproteolytically activating transcription factors Stp1 and Stp2 (Stp1/2). processing endoprotease Ssy5 is regulated via proteasomal degradation of its noncovalently associated N-terminal prodomain. We find that the prodomain requires conserved phosphodegron comprising phosphoacceptor sites ubiquitin-accepting lysine residues. Upon acid...
The highly conserved protease Lon has important regulatory and protein quality control functions in cells from the three domains of life. Despite many years research on Lon, only a few specific substrates are known most organisms. Here, we used quantitative proteomics approach to identify novel dimorphic bacterium Caulobacter crescentus. We focused our study proteins involved polar cell differentiation investigated developmental regulator StaR flagella hook length FliK as detail. show that...
Extracellular amino acids induce the yeast SPS sensor to endoproteolytically cleave transcription factors Stp1 and Stp2 in a process termed receptor-activated proteolysis (RAP). Ssy5, activating endoprotease, is synthesized with large N-terminal prodomain C-terminal chymotrypsin-like catalytic (Cat) domain. During biogenesis, Ssy5 cleaves itself Cat domain remain associated, forming an inactive primed protease. Here we show that potent inhibitor of activity its inactivation requisite for...
The Ssy1-Ptr3-Ssy5 (SPS)-sensing pathway enables yeast to respond extracellular amino acids. Stp1, the effector transcription factor, is synthesized as a latent cytoplasmic precursor with an N-terminal regulatory domain that restricts its nuclear accumulation. negative mechanisms impinging on are poorly understood. However, Stp1 latency depends three inner membrane proteins, Asi1, Asi2, and Asi3. We report of contains small motif, designated RI, fully accounts for latency. RI modular,...
Phosphoinositide lipids provide spatial landmarks during polarized cell growth and migration. Yet how phosphoinositide gradients are oriented in response to extracellular cues environmental conditions is not well understood. Here, we elucidate an unexpected mode of phosphatidylinositol 4-phosphate (PI4P) regulation the control secretion.We show that PI4P highly enriched at plasma membrane growing daughter cells budding yeast where secretion occurs. However, upon heat stress redirect...
Ligand-induced conformational changes of plasma membrane receptors initiate signals that enable cells to respond discrete extracellular cues. In response amino acids, the yeast Ssy1-Ptr3-Ssy5 sensor triggers endoproteolytic processing transcription factors Stp1 and Stp2 induce acid uptake. Activation protease Ssy5 depends on signal-induced phosphorylation its prodomain by casein kinase I (Yck1/2). Phosphorylation is required for subsequent Skp1/Cullin/Grr1 E3 ubiquitin ligase–dependent...
The Saccharomyces cerevisiae Ssy5 signaling protease is a core component of the plasma membrane (PM)-localized SPS (Ssy1-Ptr3-Ssy5) sensor. In response to extracellular amino acids, SPS-sensor orchestrates proteasomal degradation inhibitory prodomain. unfettered catalytic (Cat)-domain cleaves latent transcription factors Stp1 and Stp2, freeing them from negative N-terminal regulatory domains. By studying spatial temporal constraints affecting Cat-domain, we found that it can cleave...
Regulated protein degradation is a critical process in all cell types, which contributes to the precise regulation of amounts response internal and external cues. In bacteria, carried out by ATP-dependent proteases. Although past work revealed detailed insights into operation principles these proteases, there limited knowledge about substrate proteins that are degraded distinct proteases regulatory role proteolysis cellular processes. This study reveals direct conserved protease Lon regulating σ
Abstract 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 plasma membrane growing daughter cells. Upon heat shock however, rapidly increases mother cells resulting more uniform distribution. Rather than phosphoinositide kinase activation, hydrolysis impaired to generate heat-induced signal This fine tune mediated...
Abstract The Lon protease is a highly conserved protein degradation machine that has critical regulatory and quality control functions in cells from the three domains of life. Here, we report discovery α-proteobacterial heat shock protein, LarA, as dedicated regulator. We show LarA accumulates at onset proteotoxic stress allosterically activates Lon-catalysed large group substrates through five amino acid sequence its C-terminus. Further, find regulated by itself, which to prevent toxic...
Abstract The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer that function at contacts between the endoplasmic reticulum and plasma membrane (ER-PM contacts). However, roles of E-Syt family members in PM organisation remain unclear. Among family, yeast tricalbin (Tcb) essential for integrity upon heat stress, but it is not known how they contribute to maintenance. Using quantitative lipidomics microscopy, we find Tcb regulate...