The intracellular domain of the human protocadherin hFat1 interacts with Homer signalling scaffolding proteins

Abstract

The cadherin superfamily protein Fat1 is known to interact with the EVH1 domain of mammalian Ena/VASP. Here we demonstrate that: (i) the scaffolding proteins Homer-3 and Homer-1 also interact with the EVH1 binding site of hFat1 in vitro, and (ii) binding of Homer-3 and Mena to hFat1 is mutually competitive. Endogenous Fat1 binds to immobilised Homer-3 and endogenous Homer-3 binds to immobilised Fat1. Both, endogenous and over-expressed Fat1 exhibit co-localisation with Homer-3 in cellular protrusions and at the plasma membrane of HeLa cells. As Homer proteins and Fat1 have been both linked to psychic disorders, their interaction may be of patho-physiological importance.