BioEssays最新文献

Epithelial tissues serve as critical barriers in metazoan organisms, maintaining structural integrity and facilitating essential physiological functions. Epithelial cell polarity regulates mechanical properties, signaling, and transport, ensuring tissue organization and homeostasis. However, the barrier function is challenged by cell turnover during development and maintenance. To preserve tissue integrity while removing dying or unwanted cells, epithelial tissues employ cell extrusion. This process removes both dead and live cells from the epithelial layer, typically causing detached cells to undergo apoptosis. Transformed cells, however, often resist apoptosis, leading to multilayered structures and early carcinogenesis. Malignant cells may invade neighboring tissues. Loss of cell polarity can lead to multilayer formation, cell extrusion, and invasion. Recent studies indicate that multilayer formation in epithelial cells with polarity loss involves a mixture of wild-type and mutant cells, leading to apical or basal accumulation. The directionality of accumulation is regulated by mutations in polarity complex genes. This phenomenon, distinct from traditional apical or basal extrusion, exhibits similarities to the endophytic or exophytic growth observed in human tumors. This review explores the regulation and implications of these phenomena for tissue biology and disease pathology.

Myotonic dystrophy type 1 (DM1) is considered a progeroid disease (i.e., causing premature aging). This hypervariable disease affects multiple systems, such as the musculoskeletal, central nervous, gastrointestinal, and others. Despite advances in understanding the underlying pathogenic mechanism of DM1, numerous gaps persist in our understanding, hindering elucidation of the heterogeneity and severity of its symptoms. Accumulating evidence indicates that the toxic intracellular RNA accumulation associated with DM1 triggers cellular senescence. These cells are in a state of irreversible cell cycle arrest and secrete a cocktail of cytokines, referred to as a senescence-associated secretory phenotype (SASP), that can have harmful effects on neighboring cells and more broadly. We hypothesize that cellular senescence contributes to the pathophysiology of DM1, and clearance of senescent cells is a promising therapeutic approach for DM1. We will discuss the therapeutic potential of different senotherapeutic drugs, especially senolytics that eliminate senescent cells, and senomorphics that reduce SASP expression.

Neuropeptides are key modulators of adult neurocircuits, balancing their sensitivity to both excitation and inhibition, and fine-tuning fast neurotransmitter action under physiological conditions. Here, we reason that transient increases in neuropeptide availability and action exist during brain development for synapse maturation, selection, and maintenance. We discuss fundamental concepts of neuropeptide signaling at G protein-coupled receptors (GPCRs), with a particular focus on how signaling at neuropeptide GPCRs could underpin neuronal morphogenesis. We use galanin, a 29/30 amino acid-long neuropeptide, as an example for its retrograde release from the dendrites of thalamic neurons to impact the selection and wiring of sensory afferents originating at the trigeminal nucleus through galanin receptor 1 (GalR₁) engagement. Thus, we suggest novel roles for neuropeptides, expressed transiently or permanently during both pre- and postnatal neuronal circuit development, with potentially life-long effects on circuit layout and ensuing behavioral operations.

In this review, we introduce the concept of "dual thermosensing mechanisms," highlighting the functional collaboration between G protein-coupled receptors (GPCRs) and transient receptor potential (TRP) channels that enable sophisticated cellular thermal responsiveness. GPCRs have been implicated in thermosensory processes, with recent findings identifying several candidates across species, including mammals, fruit flies, and nematodes. In many cases, these GPCRs work in conjunction with another class of thermosensors, TRP channels, offering insights into the complex mechanisms underlying thermosensory signaling. We examine how GPCRs function as thermosensors and how their signaling regulates cellular thermosensation, illustrating the complexity of thermosensory systems. Understanding these dual thermosensory mechanisms would advance our comprehension of cellular thermosensation and its regulatory pathways.

Circadian rhythms are ∼24-h biological oscillations that enable organisms to anticipate daily environmental cycles, so that they may designate appropriate day/night functions that align with these changes. The molecular clock in animals and fungi consists of a transcription-translation feedback loop, the plant clock is comprised of multiple interlocking feedback-loops, and the cyanobacterial clock is driven by a phosphorylation cycle involving three main proteins. Despite the divergent core clock mechanisms across these systems, all circadian clocks are able to buffer period length against changes in the ambient growth environment, such as temperature and nutrients. This defining capability, termed compensation, is critical to proper timekeeping, yet the underlying mechanism(s) remain elusive. Here we examine the known players in, and the current models for, compensation across five circadian systems. While compensation models across these systems are not yet unified, common themes exist across them, including regulation via temperature-dependent changes in post-translational modifications.

Organismal death has long been considered the irreversible ending of an organism's integrated functioning as a whole. However, the persistence of functionality in organs, tissues, and cells postmortem, as seen in organ donation, raises questions about the mechanisms underlying this resilience. Recent research reveals that various factors, such as environmental conditions, metabolic activity, and inherent survival mechanisms, influence postmortem cellular functionality and transformation. These findings challenge our understanding of life and death, highlighting the potential for certain cells to grow and form new multicellular entities. This opens new avenues in biology and medicine, expanding our comprehension of life's complexity.

Daily rhythms in the rate and specificity of protein synthesis occur in most mammalian cells through an interaction between cell-autonomous circadian regulation and daily cycles of systemic cues. However, the overall protein content of a typical cell changes little over 24 h. For most proteins, translation appears to be coordinated with protein degradation, producing phases of proteomic renewal that maximize energy efficiency while broadly maintaining proteostasis across the solar cycle. We propose that a major function of this temporal compartmentalization-and of circadian rhythmicity in general-is to optimize the energy efficiency of protein synthesis and associated processes such as complex assembly. We further propose that much of this temporal compartmentalization is achieved at the level of translational initiation, such that the translational machinery alternates between distinct translational mechanisms, each using a distinct toolkit of phosphoproteins to preferentially recognize and translate different classes of mRNA.

Several recently discovered small proteins of less than 100 amino acids control important, but sometimes surprising, steps in the metabolism of cyanobacteria. There is mounting evidence that a large number of small protein genes have also been overlooked in the genome annotation of many other microorganisms. Although too short for enzymatic activity, their functional characterization has frequently revealed the involvement in processes such as signaling and sensing, interspecies communication, stress responses, metabolism, regulation of transcription and translation, and in the formation of multisubunit protein complexes. Cyanobacteria are the only prokaryotes that perform oxygenic photosynthesis. They thrive under a wide variety of conditions as long as there is light and must cope with dynamic changes in the environment. To acclimate to these fluctuations, frequently small regulatory proteins become expressed that target key enzymes and metabolic processes. The consequences of their actions are profound and can even impact the surrounding microbiome. This review highlights the diverse functions of recently discovered small proteins that control cyanobacterial metabolism. It also addresses why many of these proteins have been overlooked so far and explores the potential for implementing metabolic engineering strategies to improve the use of cyanobacteria in biotechnological applications.

The retinal pigment epithelium (RPE) is a specialized epithelium at the back of the eye that carries out a variety of functions essential for visual health. Recent studies have advanced our molecular understanding of one of the major functions of the RPE; phagocytosis of spent photoreceptor outer segments (POS). Notably, a mechanical link, formed between apical integrins bound to extracellular POS and the intracellular actomyosin cytoskeleton, is proposed to drive the internalization of POS. The process may involve a “nibbling” action, as an initial step, to sever outer segment tips. These insights have led us to hypothesize an “integrin adhesome-like” network, atypically assembled at apical membrane RPE-POS contacts. I propose that this hypothetical network orchestrates the complex membrane remodeling events required for particle internalization. Therefore, its analysis and characterization will likely lead to a more comprehensive understanding of the molecular mechanisms that control POS phagocytosis.