EphA2 signaling following endocytosis: Role of Tiam-1

Boissier, Pomme; Chen, Jin; Huynh-Do, Uyen (2013). EphA2 signaling following endocytosis: Role of Tiam-1. Traffic, 14(12), pp. 1255-1271. Wiley-Blackwell 10.1111/tra.12123

[img] Text
2013_Traffic_EphA2 Tiam1.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (35MB) | Request a copy

Eph receptors and their membrane-bound ligands, the ephrins, represent a complex subfamily of receptor tyrosine kinases (RTKs). Eph/ephrin binding can lead to various and opposite cellular behaviors such as adhesion versus repulsion, or cell migration versus cell-adhesion. Recently, Eph endocytosis has been identified as one of the critical steps responsible for such diversity. Eph receptors, as many RTKs, are rapidly endocytosed following ligand-mediated activation and traffic through endocytic compartments prior to degradation. However, it is becoming obvious that endocytosis controls signaling in many different manners. Here we showed that activated EphA2 are degraded in the lysosomes and that about 35% of internalized receptors are recycled back to the plasma membrane. Our study is also the first to demonstrate that EphA2 retains the capacity to signal in endosomes. In particular, activated EphA2 interacted with the Rho family GEF Tiam1 in endosomes. This association led to Tiam1 activation, which in turn increased Rac1 activity and facilitated Eph/ephrin endocytosis. Disrupting Tiam1 function with RNA interference impaired both ephrinA1-dependent Rac1 activation and ephrinA1-induced EphA2 endocytosis. In summary, our findings shed new light on the regulation of EphA2 endocytosis, intracellular trafficking and signal termination and establish Tiam1 as an important modulator of EphA2 signaling.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Boissier, Pomme and Huynh-Do, Uyen

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1398-9219

Publisher:

Wiley-Blackwell

Funders:

[UNSPECIFIED] Swiss National Science Foundation

Language:

English

Submitter:

Uyen Huynh-Do

Date Deposited:

22 Apr 2014 17:55

Last Modified:

25 Nov 2015 09:13

Publisher DOI:

10.1111/tra.12123

BORIS DOI:

10.7892/boris.42590

URI:

https://boris.unibe.ch/id/eprint/42590

Actions (login required)

Edit item Edit item
Provide Feedback