Naslov
PKA phosphorylation of NDE1: Links between DISC1-interacting proteins

Autori
Bradshaw, Nicholas J. ; Ogawa, F. ; Christie, Sheila ; Porteous, David J. ; Millar, J. Kirsty

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

Skup
The Molecular Basis of Schizophrenia and Bipolar Disorder (X1)

Mjesto i datum
Keystone (CO), Sjedinjene Američke Države, 06.03.2009. - 09.03.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
DISC1 ; PDE4 ; LIS1 ; NDEL1 ; NDE1 ; Schizophrenia ; Centrosome ; Synapse

Sažetak
Disrupted-In-Schizophrenia 1 (DISC1) is among the most promising schizophrenia candidate genes identified to date. The DISC1 protein appears to act as a molecular scaffold and binds to a large number of protein interactors, including Nuclear Distribution Factor E homolog 1 (NDE1) and NDE-Like 1 (NDEL1). NDE1 and NDEL1 are highly similar proteins known to play important roles in neurodevelopment. There is evidence to suggest that both are schizophrenia candidate genes in their own right. Phosphodiesterase 4B (PDE4B) is an additional DISC1 interactor that has previously been implicated as a schizophrenia risk factor by several studies. PDE4 proteins are responsible for degrading the secondary messenger cAMP. This is regulated by a negative feedback mechanism in which PDE4 is activated through phosphorylation by cAMP-dependant Protein Kinase A (PKA). We have recently demonstrated that NDE1 and NDEL1 associate with DISC1 and PDE4B at the centrosome, and most likely at the synapse also. This complexing of multiple proteins implicated as schizophrenia risk factors implies that molecular mechanisms involving these proteins are likely to be of critical importance in some cases of psychiatric illness. We are now exploring functional links between these proteins, through phosphorylation of NDE1 by PKA, a process that may be modulated by PDE4B. We have identified a site of PKA phosphorylation on NDE1, and provide evidence that the phosphorylation status of this site influences protein complexes. PKA phosphorylation of NDE1 is thus likely to regulate the cellular function of both NDE1 and NDEL1.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija

POVEZANOST RADA