Meeting details menu

Meeting Authors
Meeting Abstracts
Keynote lectures
Oral communications
Poster presentations
Special symposia
Other

Acta Physiologica Congress

Back

Acta Physiologica 2009; Volume 197, Supplement 672
The 60th National Congress of the Italian Physiological Society
9/23/2009-9/25/2009
Siena, Italy


A PDZ PROTEIN TARGET SEQUENCE AND A CLATHRIN-DEPENDENT ENDOCYTOSIS SIGNAL CONCUR IN REGULATING THE SURFACE EXPRESSION OF THE GLUTAMATE TRANSPORTER EAAC1 IN EPITHELIAL CELLS
Abstract number: P58

DI CAIRANO E, FANTIN1 G, D'AMICO1 A, SORAGNA1 A, PANZERI1 N, SACCHI1 VF, PEREGO1 C

1Dip. Scienze Mol. Applicate ai Biosistemi. Universit degli Studi di Milano; (Italy)[email protected]

Aim: 

The glutamate transporter EAAC1/EAAT3 mediates the uptake of glutamate from the synaptic cleft as well as the absorption of dicarboxylic amino acids in epithelial cells. Its cell-surface density is regulated by constitutive cycling, but the precise molecular mechanisms underlying this event are far from clear.

Methods: 

We identified a conserved consensus sequence (-SQF) for interactions with class I PDZ domains and a non-conventional tyrosine-based internalisation signal (-YVNG-) in the C-terminus of EAAC1, and investigated their role in transporter localisation in epithelial cells.

Results: 

Removal or manipulations of the PDZ-interacting sequence affected the cell surface expression of the transporter without altering its apical targeting or substrate affinity. Decreased cell surface expression was caused by faster internalisation and was prevented by hypertonic treatment or the overexpression of dominant-negative dynamine-K44A and the m2-W421A-subunit of AP-2 clathrin-adaptor. The endocytosis rate was dramatically attenuated following tyrosine mutagenesis in the internalisation signal, thus indicating that this motif can control the transporter's constitutive endocytosis.

Conclusion: 

We suggest that EAAC1 density is controlled by balanced interactions with PDZ- and clathrin-adaptor proteins: the former retain the transporter at the cell surface, and the latter promote its constitutive endocytosis.

To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 197, Supplement 672 :P58

Our site uses cookies to improve your experience.You can find out more about our use of cookies in our standard cookie policy, including instructions on how to reject and delete cookies if you wish to do so.

By continuing to browse this site you agree to us using cookies as described in our standard cookie policy .

CLOSE