Naslov
DISC1, PDE4B, and NDE1 at the centrosome and synapse

Autori
Bradshaw, Nicholas J. ; Ogawa, Fumiaki ; Antolin-Fontes, Beatriz ; Chubb, Jennifer E. ; Carlyle, Becky C. ; Christie, Sheila ; Claessens, Antoine ; Porteous, David J. ; Millar, J. Kirsty

Izvornik
Biochemical and biophysical research communications (0006-291X) 377 (2008), 4; 1091-1096

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

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

Sažetak
Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously suggested to be synaptic, and we now demonstrate localisation of DISC1, NDE1, and PDE4B at synapses in cultured neurons. NDE1 is phosphorylated by cAMP-dependant Protein Kinase A (PKA), whose activity is, in turn, regulated by the cAMP hydrolysis activity of phosphodiesterases, including PDE4. We propose that DISC1 acts as an assembly scaffold for all of these proteins and that the NDE1/ NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija

POVEZANOST RADA