Disrupted in schizophrenia 1 (DISC1): subcellular targeting and induction of ring mitochondria.
Several independent studies have identified Disrupted In Schizophrenia 1 (DISC1) as a potential susceptibility factor in the pathogenesis of schizophrenia and severe recurrent major depression. To identify potential mechanisms by which DISC1 may influence development of psychiatric illness, we investigated the cellular consequences of recombinant DISC1 expression in COS-7 cells. We show that the N-terminal head domain is sufficient for DISC1 mitochondrial and nuclear targeting, while sequence from the C-terminus facilitates centrosomal association. Loss of C-terminal sequence alters DISC1 subcellular distribution, significantly increasing nuclear localization. DISC1 over-expression produces striking mitochondrial reorganization in some cells, with formation of mitochondrial ring-like structures, indicating a potential involvement of DISC1 in mitochondrial fusion and/or fission.
Millar
J Kirsty
JK
Medical Genetics Section, Department of Medical Sciences, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Kirsty.Millar@ed.ac.uk
James
Rachel
R
Christie
Sheila
S
Porteous
David J
DJ
D000818:Animals; D019556:COS Cells; D002451:Cell Compartmentation / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D019069:Cell Respiration / Q000235:genetics; D018385:Centrosome / Q000378:metabolism; D002522:Chlorocebus aethiops; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D014407:Tumor Cells, Cultured
C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins