The role of Golgi complex proteins in cell division and consequences of their dysregulation.

The GC (Golgi complex) plays a pivotal role in the trafficking and sorting of proteins and lipids until they reach their final destination. Additionally, the GC acts as a signalling hub to regulate a multitude of cellular processes, including cell polarity, motility, apoptosis, DNA repair and cell division. In light of these crucial roles, the GC has garnered increasing attention, particularly given the evidence that a dysregulation of GC-regulated signalling pathways may contribute to the onset of various pathological conditions.

Identification and characterization of a new potent inhibitor targeting CtBP1/BARS in melanoma cells.

Background: The C-terminal-binding protein 1/brefeldin A ADP-ribosylation substrate (CtBP1/BARS) acts both as an oncogenic transcriptional co-repressor and as a fission inducing protein required for membrane trafficking and Golgi complex partitioning during mitosis, hence for mitotic entry. CtBP1/BARS overexpression, in multiple cancers, has pro-tumorigenic functions regulating gene networks associated with "cancer hallmarks" and malignant behavior including: increased cell survival, proliferation, migration/invasion, epithelial-mesenchymal transition (EMT). Structurally, CtBP1/BARS belongs to the hydroxyacid-dehydrogenase family and possesses a NAD(H)-binding Rossmann fold, which, depending on ligands bound, controls the oligomerization of CtBP1/BARS and, in turn, its cellular functions.

The Golgi checkpoint: Golgi unlinking during G2 is necessary for spindle formation and cytokinesis.

Entry into mitosis requires not only correct DNA replication but also extensive cell reorganization, including the separation of the Golgi ribbon into isolated stacks. To understand the significance of pre-mitotic Golgi reorganization, we devised a strategy to first block Golgi segregation, with the consequent G2-arrest, and then force entry into mitosis. We found that the cells forced to enter mitosis with an intact Golgi ribbon showed remarkable cell division defects, including spindle multipolarity and binucleation.

In Vitro Methods to Investigate the Disassembly of the Golgi Ribbon During the G2-M Transition of the Cell Cycle.

The Golgi complex is the central hub of the secretory pathway. In mammalian cells, it is formed by stacks of flattened cisternae organized in a continuous membrane system, the Golgi ribbon, located near the centrosome. During G2, the Golgi ribbon is disassembled into isolated stacks that, at the onset of mitosis, are further fragmented into small tubular-vesicular clusters that disperse throughout the cytoplasm.

PARP10 Mediates Mono-ADP-Ribosylation of Aurora-A Regulating G2/M Transition of the Cell Cycle.

Intracellular mono-ADP-ribosyltransferases (mono-ARTs) catalyze the covalent attachment of a single ADP-ribose molecule to protein substrates, thus regulating their functions. PARP10 is a soluble mono-ART involved in the modulation of intracellular signaling, metabolism and apoptosis. PARP10 also participates in the regulation of the G1- and S-phase of the cell cycle.

Structural Organization and Function of the Golgi Ribbon During Cell Division.

The Golgi complex has a central role in the secretory traffic. In vertebrate cells it is generally organized in polarized stacks of cisternae that are laterally connected by membranous tubules, forming a structure known as Golgi ribbon. The steady state ribbon arrangement results from a dynamic equilibrium between formation and cleavage of the membrane tubules connecting the stacks.

Golgi Complex: A Signaling Hub in Cancer.

The Golgi Complex is the central hub in the endomembrane system and serves not only as a biosynthetic and processing center but also as a trafficking and sorting station for glycoproteins and lipids. In addition, it is an active signaling hub involved in the regulation of multiple cellular processes, including cell polarity, motility, growth, autophagy, apoptosis, inflammation, DNA repair and stress responses. As such, the dysregulation of the Golgi Complex-centered signaling cascades contributes to the onset of several pathological conditions, including cancer.

Functional Coordination among the Golgi Complex, the Centrosome and the Microtubule Cytoskeleton during the Cell Cycle.

The Golgi complex of mammalian cells is organized in a ribbon-like structure often closely associated with the centrosome during interphase. Conversely, the Golgi complex assumes a fragmented and dispersed configuration away from the centrosome during mitosis. The structure of the Golgi complex and the relative position to the centrosome are dynamically regulated by microtubules.

Corrigendum: Combinatorial Strategies to Target Molecularand Signaling Pathways to Disarm Cancer Stem Cells.

[This corrects the article DOI: 10.3389/fonc.2021.

Combinatorial Strategies to Target Molecular and Signaling Pathways to Disarm Cancer Stem Cells.

Cancer is an urgent public health issue with a very huge number of cases all over the world expected to increase by 2040. Despite improved diagnosis and therapeutic protocols, it remains the main leading cause of death in the world. Cancer stem cells (CSCs) constitute a tumor subpopulation defined by ability to self-renewal and to generate the heterogeneous and differentiated cell lineages that form the tumor bulk.

The Golgi ribbon: mechanisms of maintenance and disassembly during the cell cycle.

The Golgi complex (GC) has an essential role in the processing and sorting of proteins and lipids. The GC of mammalian cells is composed of stacks of cisternae connected by membranous tubules to create a continuous network, the Golgi ribbon, whose maintenance requires several core and accessory proteins. Despite this complex structural organization, the Golgi apparatus is highly dynamic, and this property becomes particularly evident during mitosis, when the ribbon undergoes a multistep disassembly process that allows its correct partitioning and inheritance by the daughter cells.

Organelle Inheritance Control of Mitotic Entry and Progression: Implications for Tissue Homeostasis and Disease.

The Golgi complex (GC), in addition to its well-known role in membrane traffic, is also actively involved in the regulation of mitotic entry and progression. In particular, during the G2 phase of the cell cycle, the Golgi ribbon is unlinked into isolated stacks. Importantly, this ribbon cleavage is required for G2/M transition, indicating that a "Golgi mitotic checkpoint" controls the correct segregation of this organelle.

GRASP65 controls Golgi position and structure during G2/M transition by regulating the stability of microtubules.

The mammalian Golgi apparatus is organized in the form of a ribbon-like structure positioned near the centrosome. Despite its multimodular organization, the Golgi complex is characterized by a prominent structural plasticity, which is crucial during essential physiological processes, such as the G2 phase of the cell cycle, during which the Golgi ribbon must be "unlinked" into isolated stacks to allow progression into mitosis. Here we show that the Golgi-associated protein GRASP65, which is well known for its role in Golgi stacking and ribbon formation, is also required for the organization of the microtubule cytoskeleton.

Mitotic inheritance of the Golgi complex and its role in cell division.

The Golgi apparatus plays essential roles in the processing and sorting of proteins and lipids, but it can also act as a signalling hub and a microtubule-nucleation centre. The Golgi complex (GC) of mammalian cells is composed of stacks connected by tubular bridges to form a continuous membranous system. In spite of this structural complexity, the GC is highly dynamic, and this feature becomes particularly evident during mitosis, when the GC undergoes a multi-step disassembly process that allows its correct partitioning and inheritance by daughter cells.

Alterations of Golgi organization in Alzheimer's disease: A cause or a consequence?

The Golgi apparatus is a central organelle of the secretory pathway involved in the post-translational modification and sorting of lipids and proteins. In mammalian cells, the Golgi apparatus is composed of stacks of cisternae organized in polarized manner, which are interconnected by membrane tubules to constitute the Golgi ribbon, located in the proximity of the centrosome. Besides the processing and transport of cargo, the Golgi complex is actively involved in the regulation of mitotic entry, cytoskeleton organization and dynamics, calcium homeostasis, and apoptosis, representing a signalling platform for the control of several cellular functions, including signalling initiated by receptors located at the plasma membrane.

Assays to Study the Fragmentation of the Golgi Complex During the G2-M Transition of the Cell Cycle.

The Golgi complex of mammalian cells is composed of stacks of flattened cisternae that are connected by tubules to form a continuous membrane system, also known as the Golgi ribbon. At the onset of mitosis, the Golgi ribbon is progressively fragmented into small tubular-vesicular clusters and it is reconstituted before completion of cytokinesis. The investigation of the mechanisms behind this reversible cycle of disassembly and reassembly has led to the identification of structural Golgi proteins and regulators.

Aurora-A recruitment and centrosomal maturation are regulated by a Golgi-activated pool of Src during G2.

The Golgi apparatus is composed of stacks of cisternae laterally connected by tubules to form a ribbon-like structure. At the onset of mitosis, the Golgi ribbon is broken down into discrete stacks, which then undergo further fragmentation. This ribbon cleavage is required for G2/M transition, which thus indicates that a 'Golgi mitotic checkpoint' couples Golgi inheritance with cell cycle transition.

Mechanisms and Regulation of the Mitotic Inheritance of the Golgi Complex.

In mammalian cells, the Golgi complex is structured in the form of a continuous membranous system composed of stacks connected by tubular bridges: the "Golgi ribbon." At the onset of mitosis, the Golgi complex undergoes a multi-step fragmentation process that is required for its correct partition into the dividing cells. Importantly, inhibition of Golgi disassembly results in cell-cycle arrest at the G2 stage, which indicates that accurate inheritance of the Golgi complex is monitored by a "Golgi mitotic checkpoint.

The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.

Many pathogenic bacteria utilize ADP-ribosylating toxins to modify and impair essential functions of eukaryotic cells. It has been previously reported that Neisseria meningitidis possesses an ADP-ribosyltransferase enzyme, NarE, retaining the capacity to hydrolyse NAD and to transfer ADP-ribose moiety to arginine residues in target acceptor proteins. Here we show that upon internalization into human epithelial cells, NarE gains access to the cytoplasm and, through its ADP-ribosylating activity, targets host cell proteins.

JNK2 controls fragmentation of the Golgi complex and the G2/M transition through phosphorylation of GRASP65.

In mammalian cells, the Golgi complex is composed of stacks that are connected by membranous tubules. During G2, the Golgi complex is disassembled into isolated stacks. This process is required for entry into mitosis, indicating that the correct inheritance of the organelle is monitored by a 'Golgi mitotic checkpoint'.

Cep126 is required for pericentriolar satellite localisation to the centrosome and for primary cilium formation.

Background Information: The centrosome is the primary microtubule-organising centre of animal cells and it has crucial roles in several fundamental cellular functions, including cell division, cell polarity, and intracellular transport. The mechanisms responsible for this are not completely understood.

Results: The poorly characterised protein CEP126 localises to the centrosome, pericentriolar satellites and the base of the primary cilium.

Signaling at the Golgi during mitosis.

The Golgi complex of mammalian cells is composed of interconnected stacks of flattened cisternae that form a continuous membrane system in the pericentriolar region of the cell. At the onset of mitosis, this so-called Golgi ribbon is converted into small tubular-vesicular clusters in a tightly regulated fragmentation process, which leads to a temporary loss of the physical Golgi-centrosome proximity. Mitotic Golgi breakdown is required for Golgi partitioning into the two daughter cells, cell cycle progression and may contribute to the dispersal of Golgi-associated signaling molecules.

Molecular mechanism and functional role of brefeldin A-mediated ADP-ribosylation of CtBP1/BARS.

ADP-ribosylation is a posttranslational modification that modulates the functions of many target proteins. We previously showed that the fungal toxin brefeldin A (BFA) induces the ADP-ribosylation of C-terminal-binding protein-1 short-form/BFA-ADP-ribosylation substrate (CtBP1-S/BARS), a bifunctional protein with roles in the nucleus as a transcription factor and in the cytosol as a regulator of membrane fission during intracellular trafficking and mitotic partitioning of the Golgi complex. Here, we report that ADP-ribosylation of CtBP1-S/BARS by BFA occurs via a nonconventional mechanism that comprises two steps: (i) synthesis of a BFA-ADP-ribose conjugate by the ADP-ribosyl cyclase CD38 and (ii) covalent binding of the BFA-ADP-ribose conjugate into the CtBP1-S/BARS NAD(+)-binding pocket.

Golgi complex fragmentation in G2/M transition: An organelle-based cell-cycle checkpoint.

In mammalian cells, the Golgi complex is organized into a continuous membranous system known as the Golgi ribbon, which is formed by individual Golgi stacks that are laterally connected by tubular bridges. During mitosis, the Golgi ribbon undergoes extensive fragmentation through a multistage process that is required for its correct partitioning into the daughter cells. Importantly, inhibition of this Golgi disassembly results in cell-cycle arrest at the G2 stage, suggesting that accurate inheritance of the Golgi complex is monitored by a "Golgi mitotic checkpoint.