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1. The plant endoplasmic reticulum UPRome: A repository and pathway browser for genes involved in signaling networks linked to the endoplasmic reticulum

   https://doi.org/10.1002/pld3.431  

   Herath, Venura; Connolly, Kaylee; Roach, Anna; Ausekar, Ashish; Persky, Tracy; Verchot, Jeanmarie (July 2022, Plant Direct)

   Abstract The endoplasmic reticulum (ER) houses sensors that respond to environmental stress and underly plants' adaptative responses. These sensors transduce signals that lead to changes in nuclear gene expression. The ER to nuclear signaling pathways are primarily attributed to the unfolded protein response (UPR) and are also integrated with a wide range of development, hormone, immune, and stress signaling pathways. Understanding the role of the UPR in signaling network mechanisms that associate with particular phenotypes is crucially important. While UPR‐associated genes are the subject of ongoing investigations in a few model plant systems, most remain poorly annotated, hindering the identification of candidates across plant species. This open‐source curated database provides a centralized resource of peer reviewed knowledge of ER to nuclear signaling pathways for the plant community. We provide a UPRome interactive viewer for users to navigate through the pathways and to access annotated information. The plant ER UPRome website is located athttp://uprome.tamu.edu. We welcome contributions from the researchers studying the ER UPR to incorporate additional genes into the database through the “contact us” page. 

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2. Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis

   https://doi.org/10.1146/annurev-biochem-081820-092427  

   von Zastrow, Mark; Sorkin, Alexander (June 2021, Annual Review of Biochemistry)

   null (Ed.)

   Intricate relationships between endocytosis and cellular signaling, first recognized nearly 40 years ago through the study of tyrosine kinase growth factor receptors, are now known to exist for multiple receptor classes and to affect myriad physiological and developmental processes. This review summarizes our present understanding of how endocytosis orchestrates cellular signaling networks, with an emphasis on mechanistic underpinnings and focusing on two receptor classes—tyrosine kinase and G protein–coupled receptors—that have been investigated in particular detail. Together, these examples provide a useful survey of the current consensus, uncertainties, and controversies in this rapidly advancing area of cell biology. 

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3. Proteolethargy is a pathogenic mechanism in chronic disease

   https://doi.org/10.1016/j.cell.2024.10.051  

   Dall’Agnese, Alessandra; Zheng, Ming M; Moreno, Shannon; Platt, Jesse M; Hoang, An T; Kannan, Deepti; Dall’Agnese, Giuseppe; Overholt, Kalon J; Sagi, Ido; Hannett, Nancy M; et al (January 2025, Cell)

   The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent syndromes associated with pathogenic signaling, such as diabetes and chronic inflammation, where our understanding is more limited. Here, we report that pathogenic signaling suppresses the mobility of a spectrum of proteins that play essential roles in cellular functions known to be dysregulated in these chronic diseases. The reduced protein mobility, which we call proteolethargy, was linked to cysteine residues in the affected proteins and signaling-related increases in excess reactive oxygen species. Diverse pathogenic stimuli, including hyperglycemia, dyslipidemia, and inflammation, produce similar reduced protein mobility phenotypes. We propose that proteolethargy is an overlooked cellular mechanism that may account for various pathogenic features of diverse chronic diseases. 

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4. A co-fractionation mass spectrometry-based prediction of protein complex assemblies in the developing rice aleurone-subaleurone

   https://doi.org/10.1093/plcell/koab182  

   Lee, Youngwoo; Okita, Thomas W.; Szymanski, Daniel B. (July 2021, The Plant Cell)

   Abstract Multiprotein complexes execute and coordinate diverse cellular processes such as organelle biogenesis, vesicle trafficking, cell signaling, and metabolism. Knowledge about their composition and localization provides useful clues about the mechanisms of cellular homeostasis and system-level control. This is of great biological importance and practical significance in heterotrophic rice (Oryza sativa) endosperm and aleurone–subaleurone tissues, which are a primary source of seed vitamins and stored energy. Dozens of protein complexes have been implicated in the synthesis, transport, and storage of seed proteins, lipids, vitamins, and minerals. Mutations in protein complexes that control RNA transport result in aberrant endosperm with shrunken and floury phenotypes, significantly reducing seed yield and quality. The purpose of this study was to broadly predict protein complex composition in the aleurone–subaleurone layers of developing rice seeds using co-fractionation mass spectrometry. Following orthogonal chromatographic separations of biological replicates, thousands of protein elution profiles were subjected to distance-based clustering to enable large-scale multimerization state measurements and protein complex predictions. The predicted complexes had predicted functions across diverse functional categories, including novel heteromeric RNA binding protein complexes that may influence seed quality. This effective and open-ended proteomics pipeline provides useful clues about system-level posttranslational control during the early stages of rice seed development. 

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5. Targeting peptide‐based quorum sensing systems for the treatment of gram‐positive bacterial infections

   https://doi.org/10.1002/pep2.24298  

   Milly, Tahmina A.; Tal‐Gan, Yftah (November 2022, Peptide Science)

   Abstract Bacteria utilize a cell density‐dependent communication system called quorum sensing (QS) to coordinate group behaviors. In Gram‐positive bacteria, QS involves the production of and response to auto‐inducing peptide (AIP) signaling molecules to modulate group phenotypes, including pathogenicity. As such, this bacterial communication system has been identified as a potential therapeutic target against bacterial infections. More specifically, developing synthetic modulators derived from the native peptide signal paves a new way to selectively block the pathogenic behaviors associated with this signaling system. Moreover, rational design and development of potent synthetic peptide modulators allows in depth understanding of the molecular mechanisms that drive QS circuits in diverse bacterial species. Overall, studies aimed at understanding the role of QS in microbial social behavior could result in the accumulation of significant knowledge of microbial interactions, and consequently lead to the development of alternative therapeutic agents to treat bacterial infectivity. In this review, we discuss recent advances in the development of peptide‐based modulators to target QS systems in Gram‐positive pathogens, with a focus on evaluating the therapeutic potential associated with these bacterial signaling pathways. 

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