Biology of the Cell最新文献

Tissue organization is fundamental to the form and function of most, if not all, multicellular organisms. But what specifies the precise histologic organization of cells in tissues of plants and animals is unclear. We hypothesize that a tissue code exists that is the basis for dynamic maintenance of tissue organization. Any code for tissue organization must account for how the dynamics of tissue renewal maintain histologic structure. Accordingly, we modeled the dynamics of crypt renewal to determine how the organization of cells is maintained in colonic epithelium. Specifically, we modeled spatial and temporal asymmetries of cell division and established that five simple mathematical laws ([1] timing of cell division, [2] temporal order of cell division, [3] spatial direction of cell division, [4] number of cell divisions, and [5] cell lifespan) constitute a set of biological rules for colonic epithelia. Our results indicate that these rules form the basis of precise organization of cells in colonic epithelium during continuous crypt renewal. These five laws might even provide a means to understand the mechanisms that underlie organization of other tissue types, and how genetic alterations cause tissue disorganization that leads to birth defects and tissue pathology like cancer.

Endonuclease exonuclease phosphatase domain-containing protein 1 (EEPD1) is a DNase1 superfamily member that has DNA endonuclease activity. It plays a critical role in multiple DNA repair processes such as oxidative damage repair and stressed replication fork repair. Interestingly, EEPD1 is myristoylated and palmitoylated near its amino terminus in response to high levels of cholesterol, and this localizes EEPD1 protein to the inner cell membrane. Surprisingly, we found that EEPD1 promotes cortical branching actin polymerization and proper lamellipodia formation and is necessary for subsequent cell migration. EEPD1's enhancement of actin polymerization partially required its myristoylation and palmitoylation. EEPD1 depletion also resulted in marked abnormalities in nuclear morphology. Loss of EEPD1 resulted in loss of phosphorylation of SRC, RAC1, cortactin, and profilin, which are essential steps in signaling for actin polymerization. Loss of EEPD1 lowered SRC kinase activity, which would harm actin polymerization. In summary, EEPD1 is a novel, positive regulator of the signaling pathway for actin polymerization, linking actin regulation to nuclear morphology and DNA repair.

Protrusion-derived extracellular vesicles (PD-EVs) are a specialized subset of extracellular vesicles (EVs) generated from dynamic cellular extensions. These structures play a crucial role in cellular communication and have emerged as pivotal mediators in various biological processes, including cancer progression and immune modulation. In cancer, PD-EVs facilitate tumor growth, invasion, and metastasis by delivering oncogenic cargo that remodels the tumor microenvironment, promotes angiogenesis, and supports immune evasion. They are also implicated in establishing pre-metastatic niches and enabling cancer cells to colonize distant organs. PD-EVs are characterized by a distinct molecular signature linked to their origin from specialized plasma membrane domains. Their unique composition makes them promising biomarkers for early cancer detection, disease monitoring, metastatic potential assessment, and therapeutic response evaluation. Targeting PD-EV biogenesis, release, or uptake represents a novel therapeutic strategy to disrupt tumor progression and overcome resistance to current treatments. However, distinguishing PD-EVs from other EV subtypes remains challenging due to overlapping characteristics. This review consolidates the latest evidence on PD-EVs, focusing on their biogenesis, limitations in their study, functional roles in cancer, and potential applications in diagnostics and therapeutics, especially concerning immune modulation and T-cell activation.

The cell plasma membrane acts as a semi-permeable barrier essential for cellular protection and function, posing a challenge for therapeutic molecule delivery. Conventional techniques for crossing this barrier, including biophysical and biochemical methods, often exhibit limitations such as cytotoxicity and the risk of genomic integration when viral vectors are involved. In contrast, cell-penetrating peptides (CPPs) offer a promising non-invasive means to deliver a broad range of molecular cargoes, including proteins, nucleic acids and small molecules, into cells. CPPs, typically 5 to 30 amino acids long and rich in basic or non-polar residues, interact favourably with different cell membranes. These peptides have evolved since the discovery of the HIV-1 TAT peptide in the 1980s, expanding into various CPP families with diverse therapeutic applications. CPPs can form covalent or non-covalent complexes with their cargo, influencing their stability and efficacy. Based on their sequence properties and interactions, CPPs can be amphipathic or non-amphipathic, with distinct mechanisms of membrane penetration, such as direct penetration and endocytosis. While their uptake mechanisms are complex and not fully elucidated, ongoing optimization aims to enhance CPP specificity and efficacy. CPPs have demonstrated potential in drug delivery, gene therapy, cancer treatment and vaccine development, addressing key safety and efficiency concerns associated with viral vectors. This review explores the classification, mechanisms of action and therapeutic potential. It focuses on the intracellular vesicular trafficking of CPPs, highlighting their role as transformative tools in advancing cellular therapies and medical treatments.

A. Schoenit, S. Monfared, L. Anger, et al., “How Intercellular Forces Regulate Cell Competition,” Biology of the Cell 117 (2025): e70004, https://doi.org/10.1111/boc.70004

The article title has been updated from “Force transmission is a master regulator of mechanical cell competition” to “How intercellular forces regulate cell competition” to avoid confusion with the original paper it refers to.

We apologize for this error.

The auxin inducible degradation (AID) system, which allows for rapid and inducible degradation of a protein of interest, is an efficient technology to study protein function in cells. This system proves particularly useful to study cellular motors that can be involved in different mechanisms depending on the cell cycle stage. Mitotic kinesin-like protein 2 (Mklp2) is a member of the kinesin-6 family involved in intracellular trafficking both in interphase and mitosis. In mitosis, at anaphase onset, it relocates the chromosomal passenger complex (CPC), from the chromatin to the spindle midzone and equatorial cortex. Inhibition or knockdown of Mklp2 therefore leads to CPC re-localization defects and cytokinesis failure. Existing tools used to study Mklp2 functions in cells, including antibodies, siRNA, and small molecule inhibitors, allowed the identification of the general function of Mklp2 in mitosis. However, these tools induce different intermediate phenotypes during the course of mitosis, highlighting the need for an alternative Mklp2 perturbation approach. We report here a new tool to study the discrete localization of endogenous Mklp2 at different stages of the cell cycle combined with an AID tag that allows the study of the kinesin with high specificity, high efficiency, and high temporal resolution in MDCK (Madin-Darby canine kidney) epithelial cells. We show that upon auxin treatment, the acute and rapid degradation of Mklp2 results in delayed re-localization of CPC component Aurora-B to the spindle midzone during anaphase, cytokinesis failure, and cell binucleation. We validate the specificity of the system by rescuing Mklp2 expression and reversing the phenotypes. Overall, this new tool facilitates the study of endogenous Mklp2 localization and function at specific stages of the cell cycle and offers a highly specific method for exploring its roles in a nontransformed mammalian model cell line widely used to study epithelial organization and dynamics.