dc.description.abstract | The secretion of lung surfactant requires the movement of lamellar bodies to the plasma membrane through cytoskeletal barrier at the
cell cortex. We hypothesized that the cortical cytoskeleton undergoes a transient disassembly/reassembly in the stimulated type II cells,
therefore allowing lamellar bodies access to the plasma membrane. Stabilization of cytoskeleton with Jasplakinolinde (JAS), a cell
permeable actin microfilament stabilizer, caused a dose-dependent inhibition of lung surfactant secretion stimulated by terbutaline. This
inhibition was also observed in ATP-, phorbol 12-myristate 13-acetate (PMA)- or Ca2 + ionophore A23187-stimulated surfactant secretion.
Stimulation of type II cells with terbutaline exhibited a transient disassembly of filamentous actin (F-actin) as determined by staining with
Oregon Green 488 Phalloidin. The protein kinase A inhibitor, H89, abolished the terbutaline-induced F-actin disassembly. Western blot
analysis using anti-actin and anti-annexin II antibodies showed a transient increase of G-actin and annexin II in the Triton X-100 soluble
fraction of terbutaline-stimulated type II cells. Furthermore, introduction of exogenous annexin II tetramer (AIIt) into permeabilized type II
cells caused a disruption in the cortical actin. Treatment of type II cells with N-ethylmaleimide (NEM) resulted in a disruption of the
cortical actin. NEM also inhibited annexin II’s abilities to bundle F-actin. The results suggest that cytoskeleton undergoes reorganization in
the stimulated type II cells, and annexin II tetramer plays a role in this process.
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