Gene Selection, Alternative Splicing, and Post-translational Processing Regulate Neuroligin Selectivity for -Neurexin
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- 作者：Davide Comoletti ; Robyn E. Flynn ; Antony A. Boucard ; Borries Demeler ; Virgil Schirf ; Jianxin Shi ; Lori L. Jennings ; Helen R. Newlin ; Thomas C. Sü ; dhof ; Palmer Taylor
- 刊名：Biochemistry
- 出版年：2006
- 出版时间：October 24, 2006
- 年：2006
- 卷：45
- 期：42
- 页码：12816 - 12827
- 全文大小：691K
- 年卷期：v.45,no.42(October 24, 2006)
- ISSN：1520-4995
文摘
Neuroligins 1-4 are postsynaptic transmembrane proteins capable of initiating presynapticmaturation via interactions with 
-neurexin. Both neuroligins and -neurexins have alternatively splicedinserts in their extracellular domains. Using analytical ultracentrifugation, we determined that theextracellular domains of the neuroligins sediment as dimers, whereas the extracellular domains of the-neurexins appear monomeric. Sedimentation velocity experiments of titrated stoichiometry ratios of-neurexin and neuroligin suggested a 2:2 complex formation. The recognition properties of individualneuroligins toward -neurexin-1 (NX1), along with the influence of their splice inserts, were exploredby surface plasmon resonance and affinity chromatography. Different neuroligins display a range of NX1affinities spanning more than 2 orders of magnitude. Whereas splice insert 4 in -neurexin appears to actonly as a modulator of the neuroligin/-neurexin association, splice insert B in neuroligin-1 (NL1) is thekey element regulating the NL1/NX1 binding. Our data indicate that gene selection, mRNA splicing,and post-translational modifications combine to give rise to a controlled neuroligin recognition code witha rank ordering of affinities for particular neurexins that is conserved for the neuroligins across mammalianspecies.
-neurexin. Both neuroligins and -neurexins have alternatively splicedinserts in their extracellular domains. Using analytical ultracentrifugation, we determined that theextracellular domains of the neuroligins sediment as dimers, whereas the extracellular domains of the-neurexins appear monomeric. Sedimentation velocity experiments of titrated stoichiometry ratios of-neurexin and neuroligin suggested a 2:2 complex formation. The recognition properties of individualneuroligins toward -neurexin-1 (NX1), along with the influence of their splice inserts, were exploredby surface plasmon resonance and affinity chromatography. Different neuroligins display a range of NX1affinities spanning more than 2 orders of magnitude. Whereas splice insert 4 in -neurexin appears to actonly as a modulator of the neuroligin/-neurexin association, splice insert B in neuroligin-1 (NL1) is thekey element regulating the NL1/NX1 binding. Our data indicate that gene selection, mRNA splicing,and post-translational modifications combine to give rise to a controlled neuroligin recognition code witha rank ordering of affinities for particular neurexins that is conserved for the neuroligins across mammalianspecies.