Pregled bibliografske jedinice broj: 887117
DISC1/PDE4-dependent PKA phosphorylation of NDE1 modulates LIS1/NDEL1 binding and neural function
DISC1/PDE4-dependent PKA phosphorylation of NDE1 modulates LIS1/NDEL1 binding and neural function // DISC1 2010
Edinburgh, Ujedinjeno Kraljevstvo, 2010. (poster, međunarodna recenzija, sažetak, znanstveni)
CROSBI ID: 887117 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
DISC1/PDE4-dependent PKA phosphorylation of NDE1 modulates LIS1/NDEL1 binding and neural function
Autori
Bradshaw, Nicholas J. ; Soares, D. C. ; Carlyle, Becky C. ; Mackie, Shaun ; Thomson, Pippa A. ; Porteous, David J. ; Millar, J. Kirsty
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Skup
DISC1 2010
Mjesto i datum
Edinburgh, Ujedinjeno Kraljevstvo, 03.09.2010. - 06.09.2010
Vrsta sudjelovanja
Poster
Vrsta recenzije
Međunarodna recenzija
Ključne riječi
DISC1 ; PDE4 ; LIS1 ; NDEL1 ; NDE1 ; Schizophrenia ; Centrosome ; Synapse
Sažetak
Nuclear Distribution factor E-homologue 1 (NDE1), Lissencephaly 1 (LIS1) and NDE-Like 1 (NDEL1) together participate in essential neurodevelopmental processes, including neuronal precursor proliferation and differentiation, neuronal migration and neurite outgrowth1, 2. NDE1/LIS1/NDEL1 associate with Disrupted In Schizophrenia 1 (DISC1), and the cAMP-hydrolyzing enzyme Phosphodiesterase 4 (PDE4)3. DISC1, PDE4, NDE1 and NDEL1 have each been implicated as risk factors for major mental illness4-7. We demonstrate that DISC1 and PDE4 modulate NDE1 phosphorylation by cAMP-dependent Protein Kinase (PKA) and identify a novel PKA substrate site on NDE1, T131. Homology modeling predicts that phosphorylation at T131 could modulate NDE1-LIS1 and NDE1-NDEL1 interactions, which we confirm experimentally. DISC1/PDE4 thus modulates organization of the NDE1/NDEL1/LIS1 complex. Phosphorylated T131 is present at the post-synaptic density, in proximal axons, within the nucleus, and at the centrosome where it becomes substantially enriched during mitosis. Mutation of the NDE1 T131 site to mimic PKA phosphorylation inhibits neurite outgrowth. Thus DISC1/PDE4 modulated, PKA-dependent phosphorylation of the NDE1/LIS1/NDEL1 complex regulates its neural functions and is a potential genetic and molecular mechanism in schizophrenia and related psychiatric disorders.
Izvorni jezik
Engleski
Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija
