The interaction of schizophrenia-related proteins DISC1 and NDEL1, in light of the newly identified domain structure of DISC1

DISC1 and NDEL1 are both key proteins in cortical neurodevelopment, which are each also implicated in the pathogenesis of mental illness. That the two proteins interact with each other in a functionally important manner is well established, but two distinct binding domains for NDEL1 on DISC1 have been proposed. A partial domain structure for DISC1 has recently been described, consisting of 4 structured regions referred to as “D,” “I,” “S” and “C” respectively, with one of the NDEL1 binding sites lying in the “C” region of DISC1. In light of this domain structure, it can be deduced that this site is the likely location at which NDEL1 binds, although the other proposed site (which lies in the DISC1 “I” and “S” regions) may indirectly impact on DISC1-NDEL1 interactions through determination of the oligomeric state of DISC1.