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Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
Gene/Protein
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Query: UMLS:C0038362 (
stomatitis
)
8,852
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Characterizing cellular factors involved in the life cycle of human immunodeficiency virus type 1 (HIV-1) is an initial step toward controlling replication of HIV-1. Actin polymerization mediated by the
Arp2
/3 complex has been found to play a critical role in some pathogens' intracellular motility. We have asked whether this complex also contributes to the viral life cycles including that of HIV-1. We have used both the acidic domains from actin-related protein (Arp) 2/3 complex-binding proteins such as the Wiscott-Aldrich syndrome protein (N-WASP) or cortactin, and siRNA directing toward
Arp2
to inhibit viral infection. HIV-1, simian immunodeficiency virus (SIV), and intracellular mature vaccinia virus (IMV) were sensitive to inhibition of the
Arp2
/3 complex, whereas MLV, HSV-1, and adenovirus were not. Interestingly, pseudotyping HIV-1 with vesicular
stomatitis
virus G protein (VSV-G) overcame this inhibition. Constitutive inhibition of the
Arp2
/3 complex in the T-cell line H9 also blocked replication of HIV-1. These data suggested the existence of an
Arp2
/3 complex-dependent event during the early phase of the life cycles of both primate lentiviruses and IMV. Inhibiting the HIV-1's ability to activate
Arp2
/3 complex could be a potential chemotherapeutic intervention for acquired immunodeficiency syndrome (AIDS).
...
PMID:Inhibiting the Arp2/3 complex limits infection of both intracellular mature vaccinia virus and primate lentiviruses. 1538 24
Cortactin is a branched actin regulator and tumor-overexpressed protein that promotes vesicular trafficking at a variety of cellular sites, including endosomes and the trans-Golgi network. To better understand its role in secretory trafficking, we investigated its function in Golgi homeostasis. Here, we report that knockdown (KD) of cortactin leads to a dramatic change in Golgi morphology by light microscopy, dependent on binding the
Arp2
/3 actin-nucleating complex. Surprisingly, there was little effect of cortactin-KD on anterograde trafficking of the constitutive cargo vesicular
stomatitis
virus glycoprotein (VSVG), Golgi assembly from endoplasmic reticulum membranes upon Brefeldin A washout, or Golgi ultrastructure. Instead, electron microscopy studies revealed that cortactin-KD cells contained a large number of immature-appearing late endosomal/lysosomal (LE/Lys) hybrid organelles, similar to those found in lysosomal storage diseases. Consistent with a defect in LE/Lys trafficking, cortactin-KD cells also exhibited accumulation of free cholesterol and retention of the retrograde Golgi cargo mannose-6-phosphate receptor in LE. Inhibition of LE maturation by treatment of control cells with Rab7 siRNA or chloroquine led to a compact Golgi morphology similar to that observed in cortactin-KD cells. Furthermore, the Golgi morphology defects of cortactin-KD cells could be rescued by removal of cholesterol-containing lipids from the media, suggesting that buildup of cholesterol-rich membranes in immature LE/Lys induced disturbances in retrograde trafficking. Taken together, these data reveal that LE/Lys maturation and trafficking are highly sensitive to cortactin-regulated branched actin assembly and suggests that cytoskeletal-induced Golgi morphology changes can be a consequence of altered trafficking at late endosomes.
...
PMID:Regulation of late endosomal/lysosomal maturation and trafficking by cortactin affects Golgi morphology. 2299 Dec
Coronins are a large family of proteins occurring in many eukaryotes. In mammals, seven coronin genes have been identified, evidencing that coronins 1 to 6 present classic coronin structure, while coronin 7 is a tandem coronin particle, without a spiral domain, although the best characterised coronin, in terms of both structure and function, is the mammalian coronin 1. It has been proven that they are related to regulation of actin dynamics, e.g. as a result of interaction with the complex of proteins
Arp2
/3. These proteins also modulate the activity of immune system cells, including lymphocyte T and B cells, neutrophils and macrophages. They are involved in bacterial infections with Mycobacterium tuberculosis, M. leprae and Helicobacter pylori and participate in the response to viral infections, e.g. infections of lymphocytic choriomeningitis virus (LCMV) and vesicular
stomatitis
Indiana virus (VSV). Also their involvement in autoimmune diseases such as lupus erythematosus has been recorded.
...
PMID:Coronins and their role in immunological phenomena. 2845 Aug 7