Yeast two-hybrid screens implicate DISC1 in brain development and function.
DISC1 is a candidate gene for involvement in the aetiology of major psychiatric illnesses including schizophrenia. We report here the results of DISC1 yeast two-hybrid screens using human foetal and adult brain libraries. Twenty-one proteins from a variety of subcellular locations were identified, consistent with observations that DISC1 occupies multiple subcellular compartments. The cellular roles of the proteins identified implicate DISC1 in several aspects of central nervous system development and function, including gene transcription, mitochondrial function, modulation of the actin cytoskeleton, neuronal migration, glutamate transmission, and signal transduction. Intriguingly, mutations in one of the proteins identified, WKL1, have been previously suggested to underlie the aetiology of catatonic schizophrenia.
Millar
J Kirsty
JK
Medical Genetics Section, Department of Medical Sciences, The University of Edinburgh, Western General Hospital, Crewe Road, EH4 2XU, Edinburgh, UK. Kirsty.Millar@ed.ac.uk
Christie
Sheila
S
Porteous
David J
DJ
D000595:Amino Acid Sequence; D001921:Brain / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000502:physiology*; D019151:Peptide Library; D012559:Schizophrenia / Q000378:metabolism; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D013329:Structure-Activity Relationship; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000378:metabolism
C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; D019151:Peptide Library