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Duplicated Gephyrin Genes Showing Distinct Tissue Distribution and Alternative Splicing Patterns Mediate Molybdenum Cofactor Biosynthesis, Glycine Receptor Clustering, and Escape Behavior in Zebrafish.
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| J. Biol. Chem. 2011 Jan 7;286 (1): 806-17. |
| H.Hirata Laboratory, Motor Neural Circuit Laboratory |
Duplicated Gephyrin Genes Showing Distinct Tissue Distribution and Alternative Splicing Patterns Mediate Molybdenum Cofactor Biosynthesis, Glycine Receptor Clustering, and Escape Behavior in Zebrafish.
Kazutoyo Ogino, Sarah L. Ramsden, Natalie Keib, Günter Schwarz, Robert J. Harvey and Hiromi Hirata
J. Biol. Chem. 2011 Jan 7;286 (1): 806-17. DOI: 10.1074/jbc.M110.125500
Gephyrin is a multifunctional protein with a relative molecular mass of 93kD that consist of three domains; G, C and E domains. Gephyrin is essential for synaptic clustering of inhibitory neurotransmitter receptors such as glycine receptors (GlyRs) and GABAA receptors as a scaffold protein. Interestingly, gephyrin is also involved in molybdenum cofactor (Moco) biosynthesis in non-neural cells, because the G and E domains have the Moco biosynthetic activity. Many splicing isoforms of gephyrin have been reported, suggesting that insertion of certain exon(s) modifies gephyrin functions. In this study, we cloned and characterized zebrafish gephyrin genes, and revealed following points.
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Zebrafish has two gephyrin genes (gphna and gphnb) due to the ancient gene duplication. |
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There are four splicing isoforms for gphna, and two for gphnb (Figure 1). |
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Although all of the six splicing isoforms have Moco biosynthetic activities, the insertion of both the C3 and C4 cassettes significantly reduces the activity. |
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gphna is expressed ubiquitously, whereas gphnb is restricted to the neuronal tissues. |
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gphna and gphnb redundantly regulate synaptic GlyR aggregation and thus touch-elicited escape behavior (Figure 2). |
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