Original Articles
Copyright ©The Author(s) 2000. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2000; 6(3): 330-334
Published online Jun 15, 2000. doi: 10.3748/wjg.v6.i3.330
Zonula occludin toxin, a microtubule binding protein
Wen-Le Wang, Rui-Liang Lu, MariaRosaria DiPierro, Alessio Fasano
Wen-Le Wang, Rui-Liang Lu, MariaRosaria DiPierro and Alessio Fasano, Center for Vaccine Development Division of Gastroenterology, University of Baltimore at Maryland, Baltimore, MD 21201, USA
Author contributions: All authors contributed equally to the work.
Correspondence to: Alessio Fasano, Division of Pediatric GI & Nutrition, Center for Vaccine Development University of Maryland School of Medicine, 685 W. Baltimore Street, Rm 480, Baltimore, MD 21201, USA. afasano@umaryland.edu
Telephone: +1-410-706-7376 Fax: +1-410-706-6205
Received: March 4, 2000
Revised: April 3, 2000
Accepted: April 25, 2000
Published online: June 15, 2000
Abstract

AIM: To investigate the interaction of Zot with microtubule.

METHODS: Zot affinity column was applied to purify Zot-binding protein(s) from crude intestinal cell lysates. After incubation at room temperature, the column was washed and the proteins bound to the Zot affinity column we re eluted by step gradient with NaCl (0.3-0.5 mol·L-1). The fractions were subjected to 6.0%-15.0% (w/v) gradient SDS-PAGE and then transferred to PVDF membrane for N-terminal sequencing. Purified Zot and tau protein were blotted by using anti-Zot or anti-tau antibodies. Finally, purified Zot was tested in an in vitro tubulin binding assay.

RESULTS: Fractions from Zot affinity column yielded two protein bands with a Mr of 60 kU and 45 kU respectively. The N-terminal sequence of the 60 kU band resulted identical to β-tubulin. Zot also cross-reacts with anti-tau antibodies. In the in vitro tubulin binding assay, Zot co-precipitate with Mt, further suggesting that Zot possesses tubulin-b inding properties.

CONCLUSION: Taken together, these results suggest that Zot regulates the permeability of intestinal tight junctions by binding to intracellular Mt, with the subsequent activation of the intracellular signaling leading to the permeabilization of intercellular tight junctions.

Keywords: microtubules; microtubule proteins; microtubule-associated proteins; intercellular junctions; vibrio cholerae; cholera toxin; zonula occluding toxin