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1. 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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2. 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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3. 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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4. Harmonizing model organism data in the Alliance of Genome Resources

   https://doi.org/10.1093/genetics/iyac022  

   Agapite, Julie; Albou, Laurent-Philippe; Aleksander, Suzanne A; Alexander, Micheal; Anagnostopoulos, Anna V; Antonazzo, Giulia; Argasinska, Joanna; Arnaboldi, Valerio; Attrill, Helen; Becerra, Andrés; et al (February 2022, Genetics)

   Wood, V (Ed.)

   Abstract The Alliance of Genome Resources (the Alliance) is a combined effort of 7 knowledgebase projects: Saccharomyces Genome Database, WormBase, FlyBase, Mouse Genome Database, the Zebrafish Information Network, Rat Genome Database, and the Gene Ontology Resource. The Alliance seeks to provide several benefits: better service to the various communities served by these projects; a harmonized view of data for all biomedical researchers, bioinformaticians, clinicians, and students; and a more sustainable infrastructure. The Alliance has harmonized cross-organism data to provide useful comparative views of gene function, gene expression, and human disease relevance. The basis of the comparative views is shared calls of orthology relationships and the use of common ontologies. The key types of data are alleles and variants, gene function based on gene ontology annotations, phenotypes, association to human disease, gene expression, protein–protein and genetic interactions, and participation in pathways. The information is presented on uniform gene pages that allow facile summarization of information about each gene in each of the 7 organisms covered (budding yeast, roundworm Caenorhabditis elegans, fruit fly, house mouse, zebrafish, brown rat, and human). The harmonized knowledge is freely available on the alliancegenome.org portal, as downloadable files, and by APIs. We expect other existing and emerging knowledge bases to join in the effort to provide the union of useful data and features that each knowledge base currently provides. 

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5. Evolutionarily Conserved and Non-Conserved Roles of Heterotrimeric Gα Proteins of Plants

   https://doi.org/10.1093/pcp/pcac045  

   Pandey, Sona; Roy Choudhury, Swarup; Ha, Chien Van; Mohanasundaram, Boominathan; Li, Mao; Dodds, Audrey (April 2022, Plant and Cell Physiology)

   Abstract Heterotrimeric G-proteins modulate multiple signaling pathways in many eukaryotes. In plants, G-proteins have been characterized primarily from a few model angiosperms and a moss. Even within this small group, they seem to affect plant phenotypes differently: G-proteins are essential for survival in monocots, needed for adaptation but are nonessential in eudicots, and are required for life cycle completion and transition from the gametophytic to sporophytic phase in the moss Physcomitrium (Physcomitrella) patens. The classic G-protein heterotrimer consists of three subunits: one Gα, one Gβ and one Gγ. The Gα protein is a catalytically active GTPase and, in its active conformation, interacts with downstream effectors to transduce signals. Gα proteins across the plant evolutionary lineage show a high degree of sequence conservation. To explore the extent to which this sequence conservation translates to their function, we complemented the well-characterized Arabidopsis Gα protein mutant, gpa1, with Gα proteins from different plant lineages and with the yeast Gpa1 and evaluated the transgenic plants for different phenotypes controlled by AtGPA1. Our results show that the Gα protein from a eudicot or a monocot, represented by Arabidopsis and Brachypodium, respectively, can fully complement all gpa1 phenotypes. However, the basal plant Gα failed to complement the developmental phenotypes exhibited by gpa1 mutants, although the phenotypes that are exhibited in response to various exogenous signals were partially or fully complemented by all Gα proteins. Our results offer a unique perspective on the evolutionarily conserved functions of G-proteins in plants. 

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