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Bridging the synaptic gap: neuroligins and neurexin I in Apis mellifera.

Biswas S, Russell RJ, Jackson CJ, Vidovic M, Ganeshina O, Oakeshott JG, Claudianos C - PLoS ONE (2008)

Bottom Line: Neurexin I and neuroligin expression was found in brain tissue, with expression present throughout development, and in most cases significantly up-regulated in adults.We show neuroligins and neurexins comprise a highly conserved molecular system with likely similar functional roles in insects as vertebrates, and with scope in the honeybee to generate substantial functional diversity through alternative splicing.Our study provides important prerequisite data for using the bee as a model for vertebrate synaptic development.

View Article: PubMed Central - PubMed

Affiliation: University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia.

ABSTRACT
Vertebrate studies show neuroligins and neurexins are binding partners in a trans-synaptic cell adhesion complex, implicated in human autism and mental retardation disorders. Here we report a genetic analysis of homologous proteins in the honey bee. As in humans, the honeybee has five large (31-246 kb, up to 12 exons each) neuroligin genes, three of which are tightly clustered. RNA analysis of the neuroligin-3 gene reveals five alternatively spliced transcripts, generated through alternative use of exons encoding the cholinesterase-like domain. Whereas vertebrates have three neurexins the bee has just one gene named neurexin I (400 kb, 28 exons). However alternative isoforms of bee neurexin I are generated by differential use of 12 splice sites, mostly located in regions encoding LNS subdomains. Some of the splice variants of bee neurexin I resemble the vertebrate alpha- and beta-neurexins, albeit in vertebrates these forms are generated by alternative promoters. Novel splicing variations in the 3' region generate transcripts encoding alternative trans-membrane and PDZ domains. Another 3' splicing variation predicts soluble neurexin I isoforms. Neurexin I and neuroligin expression was found in brain tissue, with expression present throughout development, and in most cases significantly up-regulated in adults. Transcripts of neurexin I and one neuroligin tested were abundant in mushroom bodies, a higher order processing centre in the bee brain. We show neuroligins and neurexins comprise a highly conserved molecular system with likely similar functional roles in insects as vertebrates, and with scope in the honeybee to generate substantial functional diversity through alternative splicing. Our study provides important prerequisite data for using the bee as a model for vertebrate synaptic development.

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Spatial Expression of Neuroligins and Neurexin I in the Adult Honeybee.The methodologies behind attaining these results are as described in the Figure 5 legend. Expression levels are shown relative to the house keeping gene RPL8, given an arbitrary value of 1. Expression levels were examined from the tissue of ten adults at twenty-one days of age. Standards errors were negligible and less than +/−1.22 for all experimental results. Level of gene expression in the brain expression shown in the dark purple columns marked B, wings in the light grey columns marked W, legs in the light purple columns marked L, thorax in the dark grey columns marked T and abdomen in the blue columns marked A. Raw data from the qRT-PCR experiments in Supplementary Data Table 4.
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pone-0003542-g006: Spatial Expression of Neuroligins and Neurexin I in the Adult Honeybee.The methodologies behind attaining these results are as described in the Figure 5 legend. Expression levels are shown relative to the house keeping gene RPL8, given an arbitrary value of 1. Expression levels were examined from the tissue of ten adults at twenty-one days of age. Standards errors were negligible and less than +/−1.22 for all experimental results. Level of gene expression in the brain expression shown in the dark purple columns marked B, wings in the light grey columns marked W, legs in the light purple columns marked L, thorax in the dark grey columns marked T and abdomen in the blue columns marked A. Raw data from the qRT-PCR experiments in Supplementary Data Table 4.

Mentions: qRT-PCR experiments show that all of the honeybee neuroligin genes and neurexin I are also expressed outside of the adult brain; in the thorax, legs, abdomen and wings (Figure 6, Table 4). Expression levels (relative to the housekeeping gene Ribosomal Protein L8 (RPL8)) are still significantly higher in the brain compared to other tissues for neuroligins 2–5 and neurexin I but neuroligin 1 expression is much greater in tissues outside of the brain. This suggests a putative role for neuroligin 1 in the peripheral nervous system in addition to the central nervous system, potentially with importance at neuro-muscular junctions. Furthermore, significant expression of neuroligin 1 in the wings and legs (Table 4) suggests a putative role in nerve endings responsive to sensory input. Interestingly, human neuroligin 4X displays a similar expression profile to honeybee neuroligin 1, with low levels of brain expression and higher expression levels outside of the brain [4], [74]. Human neuroligin 4X, however, has been established as a critical molecule required for proper neuro-connectivity [39], [41], [42], illustrating that the relative distribution or expression level of a gene is not necessarily informative of its functional priorities. Thus the low levels of neuroligin 1 expression in the honeybee brain may not necessarily suggest a trivial role. On another note, although neuroligins are expressed outside of the central nervous system in all characterised species, neurexin expression is strictly restricted to the human and rodent brain, suggesting that honeybee neurexin I has greater functional diversity than that seen in vertebrates.


Bridging the synaptic gap: neuroligins and neurexin I in Apis mellifera.

Biswas S, Russell RJ, Jackson CJ, Vidovic M, Ganeshina O, Oakeshott JG, Claudianos C - PLoS ONE (2008)

Spatial Expression of Neuroligins and Neurexin I in the Adult Honeybee.The methodologies behind attaining these results are as described in the Figure 5 legend. Expression levels are shown relative to the house keeping gene RPL8, given an arbitrary value of 1. Expression levels were examined from the tissue of ten adults at twenty-one days of age. Standards errors were negligible and less than +/−1.22 for all experimental results. Level of gene expression in the brain expression shown in the dark purple columns marked B, wings in the light grey columns marked W, legs in the light purple columns marked L, thorax in the dark grey columns marked T and abdomen in the blue columns marked A. Raw data from the qRT-PCR experiments in Supplementary Data Table 4.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2570956&req=5

pone-0003542-g006: Spatial Expression of Neuroligins and Neurexin I in the Adult Honeybee.The methodologies behind attaining these results are as described in the Figure 5 legend. Expression levels are shown relative to the house keeping gene RPL8, given an arbitrary value of 1. Expression levels were examined from the tissue of ten adults at twenty-one days of age. Standards errors were negligible and less than +/−1.22 for all experimental results. Level of gene expression in the brain expression shown in the dark purple columns marked B, wings in the light grey columns marked W, legs in the light purple columns marked L, thorax in the dark grey columns marked T and abdomen in the blue columns marked A. Raw data from the qRT-PCR experiments in Supplementary Data Table 4.
Mentions: qRT-PCR experiments show that all of the honeybee neuroligin genes and neurexin I are also expressed outside of the adult brain; in the thorax, legs, abdomen and wings (Figure 6, Table 4). Expression levels (relative to the housekeeping gene Ribosomal Protein L8 (RPL8)) are still significantly higher in the brain compared to other tissues for neuroligins 2–5 and neurexin I but neuroligin 1 expression is much greater in tissues outside of the brain. This suggests a putative role for neuroligin 1 in the peripheral nervous system in addition to the central nervous system, potentially with importance at neuro-muscular junctions. Furthermore, significant expression of neuroligin 1 in the wings and legs (Table 4) suggests a putative role in nerve endings responsive to sensory input. Interestingly, human neuroligin 4X displays a similar expression profile to honeybee neuroligin 1, with low levels of brain expression and higher expression levels outside of the brain [4], [74]. Human neuroligin 4X, however, has been established as a critical molecule required for proper neuro-connectivity [39], [41], [42], illustrating that the relative distribution or expression level of a gene is not necessarily informative of its functional priorities. Thus the low levels of neuroligin 1 expression in the honeybee brain may not necessarily suggest a trivial role. On another note, although neuroligins are expressed outside of the central nervous system in all characterised species, neurexin expression is strictly restricted to the human and rodent brain, suggesting that honeybee neurexin I has greater functional diversity than that seen in vertebrates.

Bottom Line: Neurexin I and neuroligin expression was found in brain tissue, with expression present throughout development, and in most cases significantly up-regulated in adults.We show neuroligins and neurexins comprise a highly conserved molecular system with likely similar functional roles in insects as vertebrates, and with scope in the honeybee to generate substantial functional diversity through alternative splicing.Our study provides important prerequisite data for using the bee as a model for vertebrate synaptic development.

View Article: PubMed Central - PubMed

Affiliation: University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia.

ABSTRACT
Vertebrate studies show neuroligins and neurexins are binding partners in a trans-synaptic cell adhesion complex, implicated in human autism and mental retardation disorders. Here we report a genetic analysis of homologous proteins in the honey bee. As in humans, the honeybee has five large (31-246 kb, up to 12 exons each) neuroligin genes, three of which are tightly clustered. RNA analysis of the neuroligin-3 gene reveals five alternatively spliced transcripts, generated through alternative use of exons encoding the cholinesterase-like domain. Whereas vertebrates have three neurexins the bee has just one gene named neurexin I (400 kb, 28 exons). However alternative isoforms of bee neurexin I are generated by differential use of 12 splice sites, mostly located in regions encoding LNS subdomains. Some of the splice variants of bee neurexin I resemble the vertebrate alpha- and beta-neurexins, albeit in vertebrates these forms are generated by alternative promoters. Novel splicing variations in the 3' region generate transcripts encoding alternative trans-membrane and PDZ domains. Another 3' splicing variation predicts soluble neurexin I isoforms. Neurexin I and neuroligin expression was found in brain tissue, with expression present throughout development, and in most cases significantly up-regulated in adults. Transcripts of neurexin I and one neuroligin tested were abundant in mushroom bodies, a higher order processing centre in the bee brain. We show neuroligins and neurexins comprise a highly conserved molecular system with likely similar functional roles in insects as vertebrates, and with scope in the honeybee to generate substantial functional diversity through alternative splicing. Our study provides important prerequisite data for using the bee as a model for vertebrate synaptic development.

Show MeSH
Related in: MedlinePlus