136 research outputs found
N-wasp Is Required For Structural Integrity Of The Blood-testis Barrier.
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N-WASP Is Required for Structural Integrity of the Blood-Testis Barrier
During spermatogenesis, the blood-testis barrier (BTB) segregates the adluminal (apical) and basal compartments in the seminiferous epithelium, thereby creating a privileged adluminal environment that allows post-meiotic spermatid development to proceed without interference of the host immune system. A key feature of the BTB is its continuous remodeling within the Sertoli cells, the major somatic component of the seminiferous epithelium. This remodeling is necessary to allow the transport of germ cells towards the seminiferous tubule interior, while maintaining intact barrier properties. Here we demonstrate that the actin nucleation promoting factor Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) provides an essential function necessary for BTB restructuring, and for maintaining spermatogenesis. Our data suggests that the N-WASP-Arp2/3 actin polymerization machinery generates branched-actin arrays at an advanced stage of BTB remodeling. These arrays are proposed to mediate the restructuring process through endocytic recycling of BTB components. Disruption of N-WASP in Sertoli cells results in major structural abnormalities to the BTB, including mis-localization of critical junctional and cytoskeletal elements, and leads to disruption of barrier function. These impairments result in a complete arrest of spermatogenesis, underscoring the critical involvement of the somatic compartment of the seminiferous tubules in germ cell maturation
The Drosophila blood brain barrier is maintained by GPCR-dependent dynamic actin structures
Formation of actin-rich structures along the lateral borders of subperineurial glial cells are induced and maintained by the G protein–coupled receptor Moody
Heart Fields: Spatial Polarity and Temporal Dynamics
In chick and mouse, heart fields undergo dynamic morphological spatiotemporal changes during heart tube formation. Here, the dynamic change in spatial polarity of such fields is discussed and a new perspective on the heart fields is proposed. The heart progenitor cells delaminate through the primitive streak and migrate in a semicircular trajectory craniolaterally forming the bilateral heart fields as part of the splanchnic mesoderm. They switch their polarity from anteroposterior to mediolateral. The anterior intestinal portal posterior descent inverts the newly formed heart field mediolateral polarity into lateromedial by 125° bending. The heart fields revert back to their original anteroposterior polarity and fuse at the midline forming a semi heart tube by completing their half circle movement. Several names and roles were assigned to different portions of the heart fields: posterior versus anterior, first versus second, and primary versus secondary heart field. The posterior and anterior heart fields define basically physical fields that form the inflow–outflow axis of the heart tube. The first and second heart fields are, in contrast, temporal fields of differentiating cardiomyocytes expressing myosin light chain 2a and undifferentiated and proliferating precardiac mesoderm expressing Isl1 gene, respectively. The two markers present a complementary pattern and are expressed transiently in all myocardial lineages. Thus, Isl1 is not restricted to a portion of the heart field or one of the two heart lineages as has been often assumed. Anat Rec, 297:175–182, 2014. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102627/1/ar22831.pd
A formin-nucleated actin aster concentrates cell wall hydrolases for cell fusion in fission yeast.
Cell-cell fusion is essential for fertilization. For fusion of walled cells, the cell wall must be degraded at a precise location but maintained in surrounding regions to protect against lysis. In fission yeast cells, the formin Fus1, which nucleates linear actin filaments, is essential for this process. In this paper, we show that this formin organizes a specific actin structure-the actin fusion focus. Structured illumination microscopy and live-cell imaging of Fus1, actin, and type V myosins revealed an aster of actin filaments whose barbed ends are focalized near the plasma membrane. Focalization requires Fus1 and type V myosins and happens asynchronously always in the M cell first. Type V myosins are essential for fusion and concentrate cell wall hydrolases, but not cell wall synthases, at the fusion focus. Thus, the fusion focus focalizes cell wall dissolution within a broader cell wall synthesis zone to shift from cell growth to cell fusion
Actin remodeling by ADF/cofilin is required for cargo sorting at the trans-Golgi network
Sorting of both soluble and integral membrane proteins is disrupted by loss of ADF/cofilin, suggesting that actin severing controls expansion of a sorting domain within the TGN
An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types
Wiskott–Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis
Tramtrack Is Genetically Upstream of Genes Controlling Tracheal Tube Size in Drosophila
The Drosophila transcription factor Tramtrack (Ttk) is involved in a wide range of developmental decisions, ranging from early embryonic patterning to differentiation processes in organogenesis. Given the wide spectrum of functions and pleiotropic effects that hinder a comprehensive characterisation, many of the tissue specific functions of this transcription factor are only poorly understood. We recently discovered multiple roles of Ttk in the development of the tracheal system on the morphogenetic level. Here, we sought to identify some of the underlying genetic components that are responsible for the tracheal phenotypes of Ttk mutants. We therefore profiled gene expression changes after Ttk loss- and gain-of-function in whole embryos and cell populations enriched for tracheal cells. The analysis of the transcriptomes revealed widespread changes in gene expression. Interestingly, one of the most prominent gene classes that showed significant opposing responses to loss- and gain-of-function was annotated with functions in chitin metabolism, along with additional genes that are linked to cellular responses, which are impaired in ttk mutants. The expression changes of these genes were validated by quantitative real-time PCR and further functional analysis of these candidate genes and other genes also expected to control tracheal tube size revealed at least a partial explanation of Ttk's role in tube size regulation. The computational analysis of our tissue-specific gene expression data highlighted the sensitivity of the approach and revealed an interesting set of novel putatively tracheal genes
Intracellular curvature-generating proteins in cell-to-cell fusion
Cell-to-cell fusion plays an important role in normal physiology and in different pathological conditions. Early fusion stages mediated by specialized proteins and yielding fusion pores are followed by a pore expansion stage that is dependent on cell metabolism and yet unidentified machinery. Because of a similarity of membrane bending in the fusion pore rim and in highly curved intracellular membrane compartments, in the present study we explored whether changes in the activity of the proteins that generate these compartments affect cell fusion initiated by protein fusogens of influenza virus and baculovirus. We raised the intracellular concentration of curvature-generating proteins in cells by either expressing or microinjecting the ENTH (epsin N-terminal homology) domain of epsin or by expressing the GRAF1 (GTPase regulator associated with focal adhesion kinase 1) BAR (Bin/amphiphysin/Rvs) domain or the FCHo2 (FCH domain-only protein 2) F-BAR domain. Each of these treatments promoted syncytium formation. Cell fusion extents were also influenced by treatments targeting the function of another curvature-generating protein, dynamin. Cell-membrane-permeant inhibitors of dynamin GTPase blocked expansion of fusion pores and dominant-negative mutants of dynamin influenced the syncytium formation extents. We also report that syncytium formation is inhibited by reagents lowering the content and accessibility of PtdIns(4,5)P2, an important regulator of intracellular membrane remodelling. Our findings indicate that fusion pore expansion at late stages of cell-to-cell fusion is mediated, directly or indirectly, by intracellular membrane-shaping proteins
An invasive podosome-like structure promotes fusion pore formation during myoblast fusion
An F-actin–enriched protrusion resembling an invasive podosome promotes fusion pore formation between muscle founder cells and fusion-competent myoblasts
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