1. Inhibition of actin polymerization by marine toxin pectenotoxin-2.
- Author
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Masatoshi Hori, Futoshi Yazama, Yasuhiro Matsuura, Ryo Yoshimoto, Takeharu Kaneda, Takeshi Yasumoto, Hiroshi Ozaki, and Hideaki Karaki
- Subjects
ACTIN depolymerizing factors ,SMOOTH muscle contraction ,PHENYLEPHRINE ,MYOSIN ,TRANSMISSION electron microscopy - Abstract
Pectenotoxin-2 (PCTX-2) is one of the polyether macrolide toxins isolated from scallops involved in diarrheic shellfish poisoning via actin depolymerization. In the present study, we examined the bioactive mechanism of PCTX-2 in smooth muscle cells and clarify mode of action of the PCTX-2-induced actin depolymerization using purified skeletal actin. PCTX-2 (300 nM-3 μM) non-selectively inhibited vascular smooth muscle contractions elicited by high K
+ or phenylephrine in a dose-dependent manner. However, elevated cytosolic Ca2+ and myosin light chain phosphorylation stimulated by high K+ were only slightly inhibited by PCTX-2. By monitoring the fluorescent intensity of pyrenyl-actin, PCTX-2 was found to inhibit both the velocity and degree of actin polymerization. The critical concentration of G-actin was linearly increased in accordance with the concentration of PCTX-2, indicating sequestration of G-actin with 1 to 1 ratio. The kinetics of F-actin depolymerization by dilution assay indicated that PCTX-2 does not sever F-actin. Transmission electron microscopic and confocal microscopic observations demonstrated that PCTX-2 selectively depolymerized filamentous actin without affecting tublin. In conclusion, PCTX-2 is a potent natural actin depolymerizer which sequesters G-actin without severing F-actin. [ABSTRACT FROM AUTHOR]- Published
- 2018
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