A brief history of nearly EV-erything - The rise and rise of extracellular vesicles.

Extracellular vesicles (EVs) are small cargo-bearing vesicles released by cells into the extracellular space. The field of EVs has grown exponentially over the past two decades; this growth follows the realisation that EVs are not simply a waste disposal system as had originally been suggested by some, but also a complex cell-to-cell communication mechanism. Indeed, EVs have been shown to transfer functional cargo between cells and can influence several biological processes.

CAMSAPs organize an acentrosomal microtubule network from basal varicosities in radial glial cells.

Neurons of the neocortex are generated by stem cells called radial glial cells. These polarized cells extend a short apical process toward the ventricular surface and a long basal fiber that acts as a scaffold for neuronal migration. How the microtubule cytoskeleton is organized in these cells to support long-range transport is unknown.

Shedding light on the cell biology of extracellular vesicles.

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material.

The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR.

Stimulation of cells with epidermal growth factor (EGF) induces internalization and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway. For continuous cell functioning, EGFR plasma membrane levels are maintained by transporting newly synthesized EGFRs to the cell surface. The regulation of this process is largely unknown.

Diversifying the secretory routes in neurons.

Nervous system homeostasis and synaptic function need dedicated mechanisms to locally regulate the molecular composition of the neuronal plasma membrane and allow the development, maintenance and plastic modification of the neuronal morphology. The cytoskeleton and intracellular trafficking lies at the core of all these processes. In most mammalian cells, the Golgi apparatus (GA) is at the center of the biosynthetic pathway, located in the proximity of the microtubule-organizing center.

The cellular prion protein PrPc is a partner of the Wnt pathway in intestinal epithelial cells.

We reported previously that the cellular prion protein (PrP(c)) is a component of desmosomes and contributes to the intestinal barrier function. We demonstrated also the presence of PrP(c) in the nucleus of proliferating intestinal epithelial cells. Here we sought to decipher the function of this nuclear pool.

BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery.

Hermansky-Pudlak syndrome (HPS) is a group of disorders characterized by the malformation of lysosome-related organelles, such as pigment cell melanosomes. Three of nine characterized HPS subtypes result from mutations in subunits of BLOC-2, a protein complex with no known molecular function. In this paper, we exploit melanocytes from mouse HPS models to place BLOC-2 within a cargo transport pathway from recycling endosomal domains to maturing melanosomes.

p63/MT1-MMP axis is required for in situ to invasive transition in basal-like breast cancer.

The transition of ductal carcinoma in situ (DCIS) to invasive breast carcinoma requires tumor cells to cross the basement membrane (BM). However, mechanisms underlying BM transmigration are poorly understood. Here, we report that expression of membrane-type 1 (MT1)-matrix metalloproteinase (MMP), a key component of the BM invasion program, increases during breast cancer progression at the in situ to invasive breast carcinoma transition.

ARF6 promotes the formation of Rac1 and WAVE-dependent ventral F-actin rosettes in breast cancer cells in response to epidermal growth factor.

Coordination between actin cytoskeleton assembly and localized polarization of intracellular trafficking routes is crucial for cancer cell migration. ARF6 has been implicated in the endocytic recycling of surface receptors and membrane components and in actin cytoskeleton remodeling. Here we show that overexpression of an ARF6 fast-cycling mutant in MDA-MB-231 breast cancer-derived cells to mimick ARF6 hyperactivation observed in invasive breast tumors induced a striking rearrangement of the actin cytoskeleton at the ventral cell surface.

Compressive stress inhibits proliferation in tumor spheroids through a volume limitation.

In most instances, the growth of solid tumors occurs in constrained environments and requires a competition for space. A mechanical crosstalk can arise from this competition. In this article, we dissect the biomechanical sequence caused by a controlled compressive stress on multicellular spheroids (MCSs) used as a tumor model system.

Microtubule acetylation regulates dynamics of KIF1C-powered vesicles and contact of microtubule plus ends with podosomes.

Microtubule dynamics are important for a variety of key cellular functions such as intracellular trafficking, adjustment of the cell surface proteome, or adhesion structure turnover. In the current study, we investigate the effects of altered microtubule acetylation levels on the subcellular distribution of kinesins and actin cytoskeletal architecture in primary human macrophages. Microtubule acetylation was altered by overexpression or siRNA-induced depletion of the acetylase MEC-17, or by blocking α-tubulin deacetylation by addition of the inhibitor tubacin.

SLK-dependent activation of ERMs controls LGN-NuMA localization and spindle orientation.

Mitotic spindle orientation relies on a complex dialog between the spindle microtubules and the cell cortex, in which F-actin has been recently implicated. Here, we report that the membrane-actin linkers ezrin/radixin/moesin (ERMs) are strongly and directly activated by the Ste20-like kinase at mitotic entry in mammalian cells. Using microfabricated adhesive substrates to control the axis of cell division, we found that the activation of ERMs plays a key role in guiding the orientation of the mitotic spindle.

Adhesion within the stem cell niches.

Growing body of evidence confirms that cell-cell and cell-extracellular matrix adhesion within stem cell niches is essential for the establishment and maintenance of niche architecture, for the generation and transmission of short-distance regulatory signals, and for controlling the frequency and nature of stem cell divisions. Recent studies demonstrated that in many stem cell niches, adhesion to support cells and/or extracellular matrix determines orientation of stem cell division plane, thereby contributing to the control of stem cell self-renewal and differentiation. Thus, although further analysis of the implicated molecular mechanisms is required, cadherin-associated and integrin-associated events appear to play essential regulatory roles in tissue-specific stem cell niches.

Beta1 integrin deletion from the basal compartment of the mammary epithelium affects stem cells.

The mammary gland epithelium comprises two major cell types: basal and luminal. Basal cells interact directly with the extracellular matrix (ECM) and express higher levels of the ECM receptors, integrins, than luminal cells. We show that deletion of beta1 integrin from basal cells abolishes the regenerative potential of the mammary epithelium and affects mammary gland development.

Correlation between Shiga toxin B-subunit stability and antigen crosspresentation: a mutational analysis.

The homopentameric B-subunit of Shiga toxin (STxB) is used as a tool to deliver antigenic peptides and proteins to the cytosolic compartment of dendritic cells (DCs). In this study, a series of interface mutants of STxB has been constructed. All mutants retained their overall conformation, while a loss in thermal stability was observed.

Rab35 regulates an endocytic recycling pathway essential for the terminal steps of cytokinesis.

Cytokinesis is the final step of cell division and leads to the physical separation of the daughter cells. After the ingression of a cleavage membrane furrow that pinches the mother cell, future daughter cells spend much of the cytokinesis phase connected by an intercellular bridge. Rab proteins are major regulators of intracellular transport in eukaryotes, and here, we report an essential role for human Rab35 in both the stability of the bridge and its final abscission.

Actin dynamics during phagocytosis.

Bacteria, apoptotic cells and other particulate material are taken up through phagocytosis, a conserved cellular function driven by actin polymerization. As reviewed here, small GTPases of the Rho family, their activators and effectors control the local reorganization of the actin cytoskeleton underneath bound particles. Remarkably, the molecular actors and regulatory mechanisms involved during phagocytosis through the FcR or the CR3 receptors are very similar to those underlying the cytoskeletal rearrangements that take place at the leading edge of motile cell and at adhesion sites, respectively.

HIV-1 Nef impairs MHC class II antigen presentation and surface expression.

HIV-1-infected cells can avoid cytotoxic T lymphocyte killing by Nef-mediated down-regulation of surface MHC I. Here, we show that HIV-1 Nef inhibits MHC II restricted peptide presentation to specific T cells and thus may affect the induction of antiviral immune responses. Nef mediates this effect by reducing the surface level of mature (i.