Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization

Nature cell biology, 7 (9), 901-908, 2005

Speaker：賴柏吟

Commentator：謝奇璋醫師

Date：2005.11.2

Time：14:10-15:00

Place：Room 601

Abstract：

  In normal anchorage-dependent cells, integrin-mediated adhesion is required for transmitting growth signals constitutively. Loss of anchorage-dependence of growth confers cells tumorogenecity. In previous study, the authors have demonstrated that cell detaching from the extracellular matrix triggers lipid raft internalization and that is regulated by integrins¹. Caveolin is one of the most reliable markers for lipid raft. However, the relationship between caveolin and integrin-regulated lipid raft internalization remains to be identified. Caveolin is a structural component of caveolae and plays numerous roles in cell, including vesicular transport, cholesterol homeostasis, and perhaps the most important, signal transduction². To understand how caveolin-1 works during cell membrane internalization, the authors observed the dynamic changes of lipid raft by confocal microscopy. Cell detachment leaded to lipid raft internalization in the company of caveolin-1. In addition, internalization of lipid raft requires the phosphorylation of caveolin-1 on Tyr 14. Caveolin-1 mediated lipid raft internalization inhibited the phosphorylation of several signal molecules such as Erk, PI(3)K, and Rac, those are essential for cell survival. These results suggest that cells being depleted of caveolin-1 have advantage in anchorage-independent growth. Thus, lose of caveolin-1 may be a novel molecular mechanism for many human neoplastic diseases.

References：

1.         Miguel A. del Pozo, et al. Integrins regulate Rac targeting by internalization of membrane domains, Science 303, 839-842, 2004.

2.         Alex W. Cohen, et al. Role of caveolae and caveolins in health and disease, Physiology Review 84, 1341-1379, 2004.