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E-cadherin evades endocytosis

E-cadherin endocytosis is blocked by IQGAP1 unless actin filaments are disrupted by Lat-A.

E-cadherin interacts with other E-cadherin molecules on neighboring cells to form cell–cell adhesions. E-cadherin that is not involved in these trans interactions is removed from the cell surface and replaced with newly synthesized molecules to maintain dynamic adhesions. Now, Izumi et al. (page 237) show that E-cadherins that are involved in trans interactions are excused from this endocytosis by small GTPases. Disruption of this system may free cells for migration.

By reconstituting endocytosis in membrane bilayers, the group shows that clathrin-dependent endocytosis removes E-cadherin that is not interacting in trans with other E-cadherins. E-cadherins engaged in trans interactions, however, activated Rac and Cdc42, which blocked their internalization. So far it is unclear how the trans interactions activate the G proteins.

The endocytic block is enhanced by IQGAP1, an effector of Rac and Cdc42. IQGAP1 cross-links actin filaments into bundles, and the group shows that F-actin is needed to inhibit endocytosis. The bundles might press up against the bilayer, thus preventing the membrane invagination needed for vesicle budding.

Because the activation of Rac strengthens cell–cell interactions, the authors plan to determine whether down-regulation of Rac at adhesion sites—and thus reactivation of endocytosis—is essential for HGF-induced cell dissociation.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Endocytosis of E-cadherin regulated by Rac and Cdc42 small G proteins through IQGAP1 and actin filaments

Genkichi Izumi, Toshiaki Sakisaka, Takeshi Baba, Shintaro Tanaka, Koji Morimoto, and Yoshimi Takai
J. Cell Biol. 2004 166: 237-248. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 617K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                            What's this?