Biology subjects

Amen, T.

Publications and source records attributed to Amen, T..

4 recordsLinked to original sources

bioRxiv2026

Tmn blocks phage spread via plasmolysis and triggers synergistic defence responses

Membrane-associated phage defences remain poorly understood. Here we characterise Tmn, a YobI-family transmembrane P-loop NTPase that protects bacteria from phage infection by establishing a plasmolysis-associated antiviral state. Upon recognising phage T2 RIIB protein, Tmn enhances ATP turnover and selectively exports Mg2+, causing rapid cytoplasmic collapse that arrests phage replication without detectable membrane depolarisation or gross leakage of the cell content. Cryo-electron microscopy shows that Tmn assembles into a decameric membrane complex with extended cytosolic arms, an uncommon architecture among P-loop NTPases. The cytosolic arms, including a solenoid-like repeat domain, mediate trigger interaction and determine specificity. In addition to its primary defence function, Tmn-driven ATP collapse activates otherwise silent ATP-depletion-sensing defences, including Gabija and Septu type I, providing a mechanistic basis for synergy among defence systems and limiting secondary phage spread. These findings demonstrate that Tmn is a membrane-integrated sensor-effector that couples phage recognition to metabolic collapse and coordinated multi-layered immunity.

microbiology↗

bioRxiv2025

Protein Kinase C positively regulates peroxisome biogenesis by promoting peroxisome-endoplasmic reticulum interaction

Peroxisomes carry out a diverse set of metabolic functions, including oxidation of very long-chained fatty acids, degradation of D-amino acids and hydrogen peroxide, and bile acid production. Many of these functions are upregulated on demand, therefore cells control peroxisome abundance, and by extension peroxisome function, in response to environmental and developmental cues. The mechanisms upregulating peroxisomes in mammalian cells have remained unclear. Here we identify a signaling regulatory network and a mechanism that coordinate cellular demand for peroxisomes and peroxisome abundance by regulating peroxisome proliferation. We show that protein kinase C (PKC) promotes peroxisome PEX11b-dependent formation. PKC activation leads to an increase in peroxisome formation, promoting peroxisome-ER contact site formation through inactivation of GSK3{beta}. We show that removal of VAPA and VAPB impairs peroxisome biogenesis and PKC regulation. Inhibition of PKC reduces peroxisome-ER interactions, leading to a decrease in peroxisome abundance. During neuronal differentiation, active PKC leads to a significant increase in peroxisome formation. We propose that peroxisomal regulation by transient active PKC signaling enables rapid and fine-tuned responses to the need for peroxisomal activity.

cell biology↗

bioRxiv2024

Synphilin-1 as a modulator of aSyn assembly

Alpha-synuclein (aSyn) is an intrinsically disordered protein that undergoes phase-separation and is associated with several neurodegenerative conditions. However, the function and the pathological role of aSyn are still elusive. Here, we modeled different types of aSyn assemblies in living cells, and developed a model that reports on gel and solid-like inclusions based on the coexpression of aSyn and synphilin-1 (Sph1). We identified striking morphological differences between aSyn-aSyn and Sph1-aSyn assemblies, characterized by distinct antibody recognition patterns, resistance to Proteinase K treatment, and protein mobilities. Importantly, we showed that the interaction between Sph1-aSyn can be manipulated, altering inclusion size and number. Sph1-aSyn interactions were central for inclusion formation and localization, and that inclusions include lysosomes and AP-1 vesicles, consistent with previous studies in human brain tissue. In total, we provide novel insight into the biology of protein aggregation, shedding light on potential therapeutic strategies that extend beyond conventional targets. Deciphering the role of Sph1 and other aSyn-interacting proteins on aSyn biology and pathobiology will be essential for treating synucleinopathies.

molecular biology↗

bioRxiv2022

Anthrax intoxication reveals that ER-Golgi membrane contact sites control the formation of plasma membrane lipid nanodomains

To promote infections, pathogens exploit host cell machineries including structural elements of the plasma membrane. Studying these interactions and identifying involved molecular players is an ideal way to gain insights into the fundamental biology of the host cell. Here, using the anthrax toxin, we screened a 1500-gene library of regulatory, cell surface, and membrane trafficking genes for their involvement in the intoxication process. We found that the ER-Golgi-localized proteins TMED2 and TMED10 are required for toxin oligomerization at the cell surface, an essential step for anthrax intoxication that depends on localization to cholesterol-rich lipid nanodomains. Further biochemical, morphological and mechanistic analyses showed that TMED2 and TMED10 are essential components of a multiprotein supercomplex that operates exchange of both cholesterol and ceramides at ER-Golgi membrane contact sites. Overall, this study of anthrax intoxication led to the discovery that lipid compositional remodelling at ER-Golgi interfaces fully controls the formation of functional membrane nanodomains at the cell surface.

cell biology↗