DISC1
Template:PBB Disrupted-in-Schizophrenia 1 or DISC1 is a protein with a wide array of functions. It participates in cell growth, movement, axonal growth and transport, neural positioning. Disruptions in DISC1 structure may play an important role at least in some cases of schizophrenia, however the evidence from genetic linkage and association studies suggests that variants of DISC1 do not play a significant role in most cases of schizophrenia, although DISC1 may be more important in bipolar disorder. In humans, this protein is encoded by the DISC1 gene.[1]
Function
This gene is situated at chromosome 1q42.1 and overlaps with DISC2 open reading frame. The gene encodes a protein with a C-terminal domain which contains multiple coiled coil motifs and a N-terminal globular domain of undefined structure. The protein is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. Among its known interaction partners are 14-3-3ε, LIS1 and NUDEL proteins and the PDE4B enzyme.[2]
DISC1 regulates the transport of LIS1/NUDEL/14-3-3ε complex through kinesin-1.
DISC1 also regulates the proliferation of embryonic and adult neural progenitor cells through the Akt / GSK3 / β-catenin pathway[3]
Clinical significance
This gene and DISC2 are disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[4]
Interactions
DISC1 has been shown to interact with a wide array of proteins. These include NDEL1,[5][6] CEP63,[5] SPTBN4,[5] EIF3A,[5] ATF4 / ATF5,[5] FEZ1,[7] MAP1A,[5] Actinin, alpha 2[5] and RANBP9.[5]
References
- ^ Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA, Devon RS, Clair DM, Muir WJ, Blackwood DH, Porteous DJ (2000). "Disruption of two novel genes by a translocation co-segregating with schizophrenia". Hum. Mol. Genet. 9 (9): 1415–23. doi:10.1093/hmg/9.9.1415. PMID 10814723.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Hennah W, Porteous D (2009). "The DISC1 pathway modulates expression of neurodevelopmental, synaptogenic and sensory perception genes". PLoS ONE. 4 (3): e4906. doi:10.1371/journal.pone.0004906. PMC 2654149. PMID 19300510.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Ming G-l, Song H (2009). "DISC1 partners with GSK3 in neurogenesis". Cell. 136 (6): 990–992, . doi:10.1016/j.cell.2009.03.005. PMID 19303839.
{{cite journal}}: CS1 maint: extra punctuation (link) - ^ "Entrez Gene: DISC1 disrupted in schizophrenia 1".
- ^ a b c d e f g h Morris, Jill A (2003). "DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation". Hum. Mol. Genet. 12 (13). England: 1591–608. doi:10.1093/hmg/ddg162. ISSN 0964-6906. PMID 12812986.
{{cite journal}}: Check date values in:|year=(help); Cite has empty unknown parameters:|laydate=,|laysummary=, and|laysource=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help); Unknown parameter|month=ignored (help) - ^ Ozeki, Yuji (2003). "Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth". Proc. Natl. Acad. Sci. U.S.A. 100 (1). United States: 289–94. doi:10.1073/pnas.0136913100. ISSN 0027-8424. PMC 140954. PMID 12506198.
{{cite journal}}: Check date values in:|year=(help); Cite has empty unknown parameters:|laydate=,|laysummary=, and|laysource=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help); Unknown parameter|month=ignored (help) - ^ Miyoshi, K (2003). "Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth". Mol. Psychiatry. 8 (7). England: 685–94. doi:10.1038/sj.mp.4001352. ISSN 1359-4184. PMID 12874605.
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Further reading
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