Frizzled 7 and PIP2 Binding by Syntenin PDZ2 Domain Supports Frizzled 7 Trafficking and Signalling

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Jul 9

PMID 27386966

Citations 22

Authors

Antonio Luis Egea-Jimenez

Rodrigo Gallardo

Abel Garcia-Pino

Ylva Ivarsson

Anna Maria Wawrzyniak

Rudra Kashyap

Remy Loris

Joost Schymkowitz

Frederic Rousseau

Pascale Zimmermann

Affiliations

Soon will be listed here.

Abstract

PDZ domain-containing proteins work as intracellular scaffolds to control spatio-temporal aspects of cell signalling. This function is supported by the ability of their PDZ domains to bind other proteins such as receptors, but also phosphoinositide lipids important for membrane trafficking. Here we report a crystal structure of the syntenin PDZ tandem in complex with the carboxy-terminal fragment of Frizzled 7 and phosphatidylinositol 4,5-bisphosphate (PIP2). The crystal structure reveals a tripartite interaction formed via the second PDZ domain of syntenin. Biophysical and biochemical experiments establish co-operative binding of the tripartite complex and identify residues crucial for membrane PIP2-specific recognition. Experiments with cells support the importance of the syntenin-PIP2 interaction for plasma membrane targeting of Frizzled 7 and c-jun phosphorylation. This study contributes to our understanding of the biology of PDZ proteins as key players in membrane compartmentalization and dynamics.

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