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DISC-1 Leu607Phe alleles differentially affect centrosomal PCM1 localization and neurotransmitter release

Molecular Psychiatry volume 14, pages 556–557 (2009)Cite this article

The putative schizophrenia susceptibility gene Disrupted-in-schizophrenia 1 (DISC-1), encodes a pleiotropic protein with many subcellular localizations and purported functions. One key role, synaptic function, is thought to be, in part, due to effects on microtubules.1 In this context a recent study has shown that DISC-1 regulates pericentriolar material 1 (PCM1; another putative schizophrenia susceptibility gene2) localization to the centrosome,3 an organelle that serves as the main microtubule organizing center, and microtubule assembly is PCM1 dependent.4 The Leu607Phe substitution is one of the few DISC-1 polymorphisms to be associated with schizophrenia-related phenotypes that is coding,5, 6 though direct evidence for its functionality is lacking.

Given the potential links between DISC-1, PCM1, the centrosome, microtubules and synapses, we wanted to determine whether the Leu607Phe polymorphism affects centrosomal PCM1 localization, microtubule dynamics or neurotransmitter release. SH-SY5Y cells were chosen as they are human, have a neuronal phenotype, and have been utilized in neurotransmitter studies. Undifferentiated SH-SY5Y cells were transfected with constructs containing V5-tagged Leu607 or V5-tagged Phe607 DISC-1. Anti-V5 and PCM1 double immunofluorescence was performed to assess differences between the variants in centrosomal PCM1 immunoreactivity. Western blots were utilized to quantify tyrosinated and detyrosinated α-tubulin, markers of dynamic and stable microtubules, respectively.7 For neurotransmitter release studies, SH-SY5Y cells were loaded with [3H] noradrenaline, and release was measured at two [K+] concentrations (5 mM and 100 mM). Further experimental details are available in Supplementary Material.

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References

  1. Camargo LM, Collura V, Rain JC, Mizuguchi K, Hermjakob H, Kerrien S et al. Mol Psychiatry 2007; 12: 74–86.

    Article  CAS  Google Scholar 

  2. Gurling HM, Critchley H, Datta SR, McQuillin A, Blaveri E, Thirumalai S et al. Arch Gen Psychiatry 2006; 63: 844–854.

    Article  Google Scholar 

  3. Kamiya A, Tan PL, Kubo K, Engelhard C, Ishizuka K, Kubo A et al. Arch Gen Psychiatry 2008; 65: 996–1006.

    Article  CAS  Google Scholar 

  4. Dammermann A, Merdes A . J Cell Biol 2002; 159: 255–266.

    Article  CAS  Google Scholar 

  5. Hodgkinson CA, Goldman D, Jaeger J, Persaud S, Kane JM, Lipsky RH et al. Am J Hum Genet 2004; 75: 862–872.

    Article  CAS  Google Scholar 

  6. Szeszko PR, Hodgkinson CA, Robinson DG, DeRosse P, Bilder RM, Lencz T et al. Biol Psychol 2008; 79: 103–110.

    Article  Google Scholar 

  7. Peris L, Thery M, Fauré J, Saoudi Y, Lafanechère L, Chilton JK et al. J Cell Biol 2006; 174: 839–849.

    Article  CAS  Google Scholar 

  8. Ma L, Liu Y, Ky B, Shughrue PJ, Austin CP, Morris JA . Geonomics 2002; 80: 662–672.

    Article  CAS  Google Scholar 

  9. Park HJ, Seo H-J, Kim H-W, Kim JS, Hwang S-Y, Seong Y-S . Exp Mol Med 2007; 39: 828–838.

    Article  CAS  Google Scholar 

  10. Bornberg-Bauer E, Rivals E, Vingron M . Nucleic Acids Res 1998; 26: 2740–2746.

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK

    S L Eastwood & P J Harrison

  2. Section on Human Neurogenetics, National Institute of Alcohol Abuse and Alcoholism, Rockville, MD, USA

    C A Hodgkinson

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  1. S L Eastwood
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  2. C A Hodgkinson
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  3. P J Harrison
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Correspondence to S L Eastwood.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Eastwood, S., Hodgkinson, C. & Harrison, P. DISC-1 Leu607Phe alleles differentially affect centrosomal PCM1 localization and neurotransmitter release. Mol Psychiatry 14, 556–557 (2009). https://doi.org/10.1038/mp.2009.13

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