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Psychiatry Newsletter - Guilt by Centrosome
Hopkins BrainWise Fall 2008
Guilt by Centrosome
Date: October 12, 2010
Centrosomes are a vague memory for most of us, a shaky freshman-biology recollection of cell parts having to do with mitosis and waving cilia, perhaps. Yet if that’s the case, an update is in order: Not only do centrosomes ready a cell’s internal scaffolding to carry out movement and transport, but now it seems they’ve a tie to psychiatric disease.
This fall, in lab mouse studies, a team led by Psychiatry’s Akira Sawa, and including Nicola Cascella and colleague Nicholas Katsanis painstakingly clarified a key centrosomal pathway and showed its likely relation to one form of schizophrenia.
Normally, the new work suggests, proteins made by three centrosomal genes—abbreviated DISC1, BBS and PCM1—interact early in some as yet unknown way in embryonic cells. The cells then migrate properly to the developing cerebral cortex.
Mutations that warp the proteins, however, appear to cause a characteristic sort of havoc. And it’s the team’s additional achievement that they saw some of that havoc as an early stage of one type of schizophrenia.
One of the mutated genes, Disrupted In Schizophrenia (DISC1), was already linked with psychiatric disease in a Scottish family—hence the name. In 2006, Sawa’s lab showed that developing mice whose brains are shortchanged of normal DISC1 mimic schizophrenia. (His group later proved DISC1 acts at the centrosome.)
The second mutant gene on its own causes Bardet-Biedl syndrome—a genetic eye and kidney disease that also can bring abnormal behavior, says Katsanis, who’s published widely on its biology. And this new study led the researchers to believe that mutation in the third gene, PCM1, may be tied more subtly to schizophrenia (article, left, on deficit disease).
“Serendipity brought us together from the corners of the campus,” says Katsanis, “and allowed us to see the links between these three proteins, centrosomes and schizophrenia.”