HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/G812    most recent 00250.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Fukushima, K. Articles by Shimosegawa, T. Search for Related Content PubMed PubMed Citation Articles by Fukushima, K. Articles by Shimosegawa, T.

NEUROREGULATION AND MOTILITY

Filopodia formation via a specific Eph family member and PI3K in immortalized cholangiocytes

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan

Submitted 31 May 2005 ; accepted in final form 24 May 2006

Biliary ducts are lined with epithelial cells, which consist of at least two types of cholangiocytes, small and large. In contrast to large cholangiocytes, which are involved in secretion, the role of small cholangiocytes has not been elucidated. To address this question, we analyzed the migration-based characteristics of these cells that may help to understand their functions in vivo. Interestingly, dibutyryl cAMP induced marked filopodia formation and cdc42 activation in the normal mouse cholangiocyte (NMC)-small cell line compared with the NMC-large cell line. Analysis of members of the ephrin (Eph)A family of guidance molecules revealed a distinct subcellular distribution of EphA5 and EphA8 members: EphA8 was equally expressed by both cell types and localized subcellularly in peripheral cell membranes, whereas EphA5 was expressed predominantly in NMC-S and localized to filopodia. Moreover, cAMP-inducible filopodia formation in these cells was abrogated using EphA5 short interfering RNA. Finally, we found that the Rho family GTPase cdc42 was activated in a manner dependent on EphA5. Wortmannin, a specific inhibitor of phosphotidylinositol 3-kinase (PI3K), abolished the activation of cdc42 dependent on EphA5, suggesting the involvement of PI3K in the EphA5-cdc42 pathway. Together, our findings suggest a cAMP-EphA5-cdc42-dependent regulation of small cholangiocyte migration, which are anticipated to facilitate the understanding of the nature of cholangiocytes and to explain certain general aspects of cAMP-cdc42 activation signaling with regard to cell morphogenesis.

ephrin; cdc42; cAMP; cell morphology; phosphotidylinositol 3-kinase