The planar cell polarity protein Vangl2 interacts with the <scp>PDZ</scp> ‐domains of Scribble but not with a unique <scp>PDZ</scp> ‐like domain in Inturned

The proteins Inturned and Fuzzy are members of the tri-longin domain (TLD) RabGEF family and activate the GTPase Rab23 downstream of the core planar cell polarity (PCP) proteins Vangl2 and Prickle. To gain insight into the function of a predicted PDZ domain unique to Inturned among TLD proteins, we performed structural and biochemical characterisations. We show that this domain does not interact with membranes or Vangl2. Instead, we find a phosphorylation-dependent interaction between Vangl2 and a PDZ domain of the apical-basal polarity protein Scribble. A crystal structure of Intu-PDZ reveals a unique PDZ-like fold lacking an interaction site for PDZ-binding motifs. Our data provide new insight into the role of PDZ domains in coordinating cell polarity downstream of Vangl2.