The Cdc42 inhibitor secramine B prevents cAMP-induced K+ conductance in intestinal epithelial cells

Pelish, Henry E.; Ciesla, William P.; Tanaka, Nori; Reddy, K. Hemachandra; Shair, Matthew D.; Kirchhausen, Tomas; Lencer, Wayne I.

doi:10.1016/j.bcp.2006.03.011

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…Alternatively, activated CDC42 and Rac1 can induce actin rearrangements independently of PAK1 [34] , [40] – [43] by direct interaction with WASP or WAVE family proteins, respectively [44] , [45] . However, inhibitors of CDC42 (Pirl1 [46] ), Rac1 (NSC23766 [47] ) or N-WASP (wiskostatin [48] ) did not display inhibitory effects on DYNA-IND or DYNA-DEP entry of IAV ( Fig. 9C–D ).…”

Section: Resultsmentioning

confidence: 96%

Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry Pathway

et al. 2011

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Influenza A virus (IAV) enters host cells upon binding of its hemagglutinin glycoprotein to sialylated host cell receptors. Whereas dynamin-dependent, clathrin-mediated endocytosis (CME) is generally considered as the IAV infection pathway, some observations suggest the occurrence of an as yet uncharacterized alternative entry route. By manipulating entry parameters we established experimental conditions that allow the separate analysis of dynamin-dependent and -independent entry of IAV. Whereas entry of IAV in phosphate-buffered saline could be completely inhibited by dynasore, a specific inhibitor of dynamin, a dynasore-insensitive entry pathway became functional in the presence of fetal calf serum. This finding was confirmed with the use of small interfering RNAs targeting dynamin-2. In the presence of serum, both IAV entry pathways were operational. Under these conditions entry could be fully blocked by combined treatment with dynasore and the amiloride derivative EIPA, the hallmark inhibitor of macropinocytosis, whereas either drug alone had no effect. The sensitivity of the dynamin-independent entry pathway to inhibitors or dominant-negative mutants affecting actomyosin dynamics as well as to a number of specific inhibitors of growth factor receptor tyrosine kinases and downstream effectors thereof all point to the involvement of macropinocytosis in IAV entry. Consistently, IAV particles and soluble FITC-dextran were shown to co-localize in cells in the same vesicles. Thus, in addition to the classical dynamin-dependent, clathrin-mediated endocytosis pathway, IAV enters host cells by a dynamin-independent route that has all the characteristics of macropinocytosis.

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Section: Resultsmentioning

confidence: 96%

Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry Pathway

et al. 2011

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“…All media were obtained from Invitrogen. Cell monolayers (passages [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] were grown on polycarbonate inserts with 0.4-m pore size (Costar, Cambridge, MA) or in plastic six-well plates for 7-14 days. Experiments were performed on confluent monolayers with transepithelial electrical resistances Ͼ 1,500 ⍀·cm 2 .…”

Section: Methodsmentioning

confidence: 99%

Enterohemorrhagic Escherichia coli infection stimulates Shiga toxin 1 macropinocytosis and transcytosis across intestinal epithelial cells

Lukyanenko¹,

Malyukova²,

Hubbard³

et al. 2011

American Journal of Physiology-Cell Physiology

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Gastrointestinal infection with Shiga toxins producing enterohemorrhagic Escherichia coli causes the spectrum of gastrointestinal and systemic complications, including hemorrhagic colitis and hemolytic uremic syndrome, which is fatal in ∼10% of patients. However, the molecular mechanisms of Stx endocytosis by enterocytes and the toxins cross the intestinal epithelium are largely uncharacterized. We have studied Shiga toxin 1 entry into enterohemorrhagic E. coli-infected intestinal epithelial cells and found that bacteria stimulate Shiga toxin 1 macropinocytosis through actin remodeling. This enterohemorrhagic E. coli-caused macropinocytosis occurs through a nonmuscle myosin II and cell division control 42 (Cdc42)-dependent mechanism. Macropinocytosis of Shiga toxin 1 is followed by its transcytosis to the basolateral environment, a step that is necessary for its systemic spread. Inhibition of Shiga toxin 1 macropinocytosis significantly decreases toxin uptake by intestinal epithelial cells and in this way provides an attractive, antibiotic-independent strategy for prevention of the harmful consequences of enterohemorrhagic E. coli infection.

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“…Cdc42 null mice are embryonic lethal and CDC42 is essential for PIP2-induced actin reorganization (Chen et al, 2000). Secramine B inhibits CDC42 (Pelish et al, 2006).…”

Section: Cdc42mentioning

confidence: 99%

Frontier of Epilepsy Research - mTOR signaling pathway

Cho

2011

Exp Mol Med

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The Cdc42 inhibitor secramine B prevents cAMP-induced K+ conductance in intestinal epithelial cells

Cited by 9 publications

References 31 publications

Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry Pathway

Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry Pathway

Enterohemorrhagic Escherichia coli infection stimulates Shiga toxin 1 macropinocytosis and transcytosis across intestinal epithelial cells

Frontier of Epilepsy Research - mTOR signaling pathway

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