BioEssays最新文献

Pluripotent stem cell lines derived from preimplantation mouse embryos have opened opportunities for the study of early mammalian development and generation of genetically uncompromised material for differentiation into specific cell types. Murine embryonic stem cells are highly versatile and can be engineered and introduced into host embryos, transferred to recipient females, and gestated to investigate gene function at multiple levels as well as developmental mechanisms, including lineage segregation and cell competition. In this review, we summarize the biomedical motivation driving the incremental modification to culture regimes and analyses that have advanced stem cell research to its current state. Ongoing investigation into divergent mechanisms of early developmental processes adopted by other species, such as agriculturally beneficial mammals and birds, will continue to enrich knowledge and inform strategies for future in vitro models.

The ability to initiate DNA replication is a critical step in the proliferation of all organisms. In bacteria, this process is mediated by an ATP-dependent replication initiator protein, DnaA, which recognizes and melts replication origin (oriC) elements. Despite decades of biochemical and structural work, a mechanistic understanding of how DnaA recognizes and unwinds oriC has remained enigmatic. A recent study by Pelliciari et al. provides important new structural insights into how DnaA from Bacillus subtilis recognizes and processes its cognate oriC, showing how DnaA uses sequence features encoded in the origin to engage melted DNA. Comparison of the DnaA-oriC structure with archaeal/eukaryl replication origin complexes based on Orc-family proteins reveals a high degree of similarity in origin engagement by initiators from di domains of life, despite fundamental differences in origin melting mechanisms. These findings provide valuable insights into bacterial replication initiation and highlight the intriguing evolutionary history of this fundamental biological process.

Neurodegenerative diseases encompass a spectrum of conditions characterized by the gradual deterioration of neurons in the central and peripheral nervous system. While their origins are multifaceted, emerging data underscore the pivotal role of impaired mitochondrial functions and endolysosomal homeostasis to the onset and progression of pathology. This article explores whether mitochondrial dysfunctions act as causal factors or are intricately linked to the decline in endolysosomal function. As research delves deeper into the genetics of neurodegenerative diseases, an increasing number of risk loci and genes associated with the regulation of endolysosomal and autophagy functions are being identified, arguing for a downstream impact on mitochondrial health. Our hypothesis centers on the notion that disturbances in endolysosomal processes may propagate to other organelles, including mitochondria, through disrupted inter-organellar communication. We discuss these views in the context of major neurodegenerative diseases including Alzheimer's and Parkinson's diseases, and their relevance to potential therapeutic avenues.

The LIM domain kinases (LIMKs) are important actin cytoskeleton regulators. These proteins, LIMK1 and LIMK2, are nodes downstream of Rho GTPases and are the key enzymes that phosphorylate cofilin/actin depolymerization factors to regulate filament severing. They therefore perform an essential role in cascades that control actin depolymerization. Signaling of the LIMKs is carefully regulated by numerous inter- and intra-molecular mechanisms. In this review, we discuss recent findings that improve the understanding of LIM domain kinase regulation mechanisms. We also provide an up-to-date review of the role of the LIM domain kinases, their architectural features, how activity is impacted by other proteins, and the implications of these findings for human health and disease.

The three-dimensional architecture of the bacterial chromosome is intertwined with genome processes such as transcription and replication. Conspicuously so, that the structure of the chromosome permits accurate prediction of active genome processes. Although appreciation of this interplay has developed rapidly in the past two decades, our understanding of this subject is still in its infancy, with research primarily focusing on how the process of transcription regulates and is regulated by chromosome structure. Here, we summarize the latest developments in the field with a focus on the interplay between chromosome structure and transcription in Escherichia coli (E. coli) as mediated by H-NS—a model nucleoid structuring protein. We describe how the organization of chromosomes at the global and local scales is dependent on transcription, and how transcription is regulated by chromosome structure. Finally, we take note of studies that highlight our limited knowledge of structure-function relationships in the chromosome, and we point out research tracks that will improve our insight in the topic.

Ever since their introduction a decade ago, stable introns, a type of noncoding (nc)RNAs, are found to be key players in different important cellular processes acting through regulation of gene expression and feedback loops to maintain cellular homeostasis. Despite being commonly regarded as useless byproducts, recent studies in yeast suggested that stable introns are essential for cell survivability under starvation. In Drosophila, we found that a stable intron, sisR-1, has a direct effect in regulating mitochondrial dynamics during short-term fasting and subsequently improved overall oocyte quality. We speculated that the beneficial effects implicated by sisR-1 is through the activation of mitohormesis, an interesting phenomenon in mitochondrial biology. Mitohormesis is suggested to improve health span and lifespan of cells and organisms, but the involvement of ncRNAs is not well-documented. Here, we discuss the potential role of sisR-1 and other ncRNAs in activating mitohormesis and the possible applications in improving cellular and organismal health.

In plants, robust defense depends on the efficient and resilient trafficking supply chains to the site of pathogen attack. Though the importance of intracellular trafficking in plant immunity has been well established, a lack of clarity remains regarding the contribution of the various trafficking pathways in transporting immune-related proteins. We have recently identified a trans-Golgi network protein, TGN-ASSOCIATED PROTEIN 1 (TGNap1), which functionally links post-Golgi vesicles with the cytoskeleton to transport immunity-related proteins in the model plant species Arabidopsis thaliana. We propose new hypotheses on the various functional implications of TGNap1 and then elaborate on the surprising heterogeneity of TGN vesicles during immunity revealed by the discovery of TGNap1 and other TGN-associated proteins in recent years.

The actin cytoskeleton is a key cellular structure subverted by pathogens to infect and survive in or on host cells. Several pathogenic strains of Escherichia coli, such as enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC), developed a unique mechanism to remodel the actin cytoskeleton that involves the assembly of actin filament-rich pedestals beneath the bacterial attachment sites. Actin pedestal assembly is driven by bacterial effectors injected into the host cells, and this structure is important for EPEC and EHEC colonization. While the interplay between bacterial effectors and the actin polymerization machinery of host cells is well-understood, how other mechanisms of actin filament remodelling regulate pedestal assembly and bacterial attachment are poorly investigated. This review discusses the gaps in our understanding of the complexity of the actin cytoskeletal remodelling during EPEC and EHEC infection. We describe possible roles of actin depolymerizing, crosslinking and motor proteins in pedestal dynamics, and bacterial interactions with the host cells. We also discuss the biological significance of pedestal assembly for bacterial infection.