Naslov
NDE1 interacts with DISC1: A link between two schizophrenia-related genes

Autori
Bradshaw, N. J. ; Christie, S. ; Mackie, S. ; Porteous D. J. ; Millar, J. K.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Skup
Neuroscience 2007

Mjesto i datum
San Diego (CA), Sjedinjene Američke Države, 03.11.2007. - 07.11.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
NDE1 ; NDEL1 ; DISC1 ; Schizophrenia ; NudE

Sažetak
In a large Scottish family a balanced chromosomal translocation co-segregates with schizophrenia, bipolar disorder and major depression. This translocation directly disrupts the Disrupted-In-Schizophrenia 1 (DISC1) gene, implicating it as a genetic risk factor. Several population studies have since provided further evidence that DISC1 confers susceptibility to psychiatric illness. A large number of confirmed or putative DISC1 interacting proteins have been identified and DISC1 is therefore believed to act as a molecular scaffold. One of the most frequently identified DISC1 interactors is NDEL1 (Nuclear Distribution factor E homolog-like 1, formerly NUDEL). NDEL1 complexes with lissencephaly-1 (LIS1), and is involved in neuronal migration, most likely the nucleokinesis step. NDEL1 association with DISC1 is developmentally regulated, implicating DISC1 and NDEL1 in neuronal development. Moreover NDEL1 expression is down regulated in post-mortem brain samples from patients diagnosed with schizophrenia, indicating that the NDEL1-DISC1 interaction is likely to be directly involved in some cases of schizophrenia. NDE1 (Nuclear Distribution factor E homolog 1, formerly NUDE) is orthologous to NDEL1 and these proteins share considerable sequence homology. The majority of studies to date have focussed on NDEL1, on the general assumption that NDEL1 and NDE1 are functionally equivalent. Consistent with this view, two yeast two-hybrid screens have identified NDE1 as a putative DISC1 interactor, and a recent genetic study in Finland identified NDE1 as a potential schizophrenia risk factor. These data suggest that a NDE1-DISC1 interaction would also be clinically relevant. We have demonstrated that NDE1 and DISC1 interact and colocalize within cells. Like NDEL1, NDE1 is apparently capable of forming a homodimer, but can also form a complex with NDEL1. However, despite these similarities, functional differences between NDEL1 and NDE1 have recently been reported and to investigate this further we have examined the phosphorylation profiles of these two proteins. Our preliminary analysis suggests important differences between NDEL1 and NDE1 phosphorylation, indicating that, despite their close homology, these proteins should be studied independently, and not assumed to be functionally equivalent.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija

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