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.

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