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The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns.

Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ - BMC Genomics (2007)

Bottom Line: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development.We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system.This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. jadolan@tcd.ie

ABSTRACT

Background: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships.

Results: This yields a total of 369 proteins (29 in worm, 66 in fly, 135 in mouse and 139 in human), many of them of unknown function. We group eLRR proteins into several classes: those with only LRRs, those that cluster with Toll-like receptors (Tlrs), those with immunoglobulin or fibronectin-type 3 (FN3) domains and those with some other domain. These groups show differential patterns of expansion and diversification across species. Our analyses reveal several clusters of novel genes, including two Elfn genes, encoding transmembrane proteins with eLRRs and an FN3 domain, and six genes encoding transmembrane proteins with eLRRs only (the Elron cluster). Many of these are expressed in discrete patterns in the developing mouse brain, notably in the thalamus and cortex. We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system.

Conclusion: This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.

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Related in: MedlinePlus

Expression of novel eLRR genes in the Drosophila embryo. (A) A lateral view of a stage 12 embryo showing expression of CG7702 in the midgut and the peripheral nervous system, PNS expression is indicated by a black arrow. (B) CG40500 expression in a stage 16 embryo, expression can be seen at the midline (indicated by a black arrow). (C and D) Lateral and ventral views, respectively, of a stage 15 embryo showing CG11910 expression in the central nervous system. (E) A stage 16 embryo with CG5888 expression in the CNS and midgut chamber, midgut chamber is indicated by a black arrow. (F) A dissected ventral nerve cord fillet with CG5888 expression (shown at 400× magnification). (G) A stage 11 embryo showing CG11136 expression at the midline, indicated by a white arrow and (H) a stage 15 embryo showing expression of CG11136 in the somatic musculature. All whole embryos are shown at 200× magnification. In all views anterior is to the left, in all lateral views dorsal is at the top, B, D and E show ventral views and G shows a dorsal view.
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Figure 10: Expression of novel eLRR genes in the Drosophila embryo. (A) A lateral view of a stage 12 embryo showing expression of CG7702 in the midgut and the peripheral nervous system, PNS expression is indicated by a black arrow. (B) CG40500 expression in a stage 16 embryo, expression can be seen at the midline (indicated by a black arrow). (C and D) Lateral and ventral views, respectively, of a stage 15 embryo showing CG11910 expression in the central nervous system. (E) A stage 16 embryo with CG5888 expression in the CNS and midgut chamber, midgut chamber is indicated by a black arrow. (F) A dissected ventral nerve cord fillet with CG5888 expression (shown at 400× magnification). (G) A stage 11 embryo showing CG11136 expression at the midline, indicated by a white arrow and (H) a stage 15 embryo showing expression of CG11136 in the somatic musculature. All whole embryos are shown at 200× magnification. In all views anterior is to the left, in all lateral views dorsal is at the top, B, D and E show ventral views and G shows a dorsal view.

Mentions: The expression patterns of many of the Drosophila eLRR genes identified in the bioinformatic screen were also examined in the embryo by in situ hybridisation. A summary of the expression patterns we identified and those previously described is presented [see Additional File 7]. We describe here the expression patterns of those novel eLRR genes identified in our survey that include expression in the nervous system (Figure 10). CG7702 is expressed dynamically in the peripheral nervous system (PNS), appearing at stage 11 and disappearing during stage 15. CG40500 is exclusively expressed in the CNS and is restricted to a subset of cells at the ventral midline, beginning during stage 14 and remaining into stage 17. CG11910 expression is restricted to the most dorsal layer of the CNS in a position consistent with the longitudinal glia. This expression begins at stage 12 and continues throughout embryonic development. CG5888 is expressed from stage 5 throughout the embryo with exception of the anterior tip (data not shown). At stage 15 expression of CG5888 is initiated in a subset of cells in the CNS. CG11136 is expressed in an anteroposterior stripe within the neurogenic region and in the prospective brain lobes during stages 8–10 (data not shown) and in discrete cells at the midline of the CNS during stages 11 and 12. From stage 11 onwards CG11136 expression is seen predominantly in the somatic musculature.


The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns.

Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ - BMC Genomics (2007)

Expression of novel eLRR genes in the Drosophila embryo. (A) A lateral view of a stage 12 embryo showing expression of CG7702 in the midgut and the peripheral nervous system, PNS expression is indicated by a black arrow. (B) CG40500 expression in a stage 16 embryo, expression can be seen at the midline (indicated by a black arrow). (C and D) Lateral and ventral views, respectively, of a stage 15 embryo showing CG11910 expression in the central nervous system. (E) A stage 16 embryo with CG5888 expression in the CNS and midgut chamber, midgut chamber is indicated by a black arrow. (F) A dissected ventral nerve cord fillet with CG5888 expression (shown at 400× magnification). (G) A stage 11 embryo showing CG11136 expression at the midline, indicated by a white arrow and (H) a stage 15 embryo showing expression of CG11136 in the somatic musculature. All whole embryos are shown at 200× magnification. In all views anterior is to the left, in all lateral views dorsal is at the top, B, D and E show ventral views and G shows a dorsal view.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2235866&req=5

Figure 10: Expression of novel eLRR genes in the Drosophila embryo. (A) A lateral view of a stage 12 embryo showing expression of CG7702 in the midgut and the peripheral nervous system, PNS expression is indicated by a black arrow. (B) CG40500 expression in a stage 16 embryo, expression can be seen at the midline (indicated by a black arrow). (C and D) Lateral and ventral views, respectively, of a stage 15 embryo showing CG11910 expression in the central nervous system. (E) A stage 16 embryo with CG5888 expression in the CNS and midgut chamber, midgut chamber is indicated by a black arrow. (F) A dissected ventral nerve cord fillet with CG5888 expression (shown at 400× magnification). (G) A stage 11 embryo showing CG11136 expression at the midline, indicated by a white arrow and (H) a stage 15 embryo showing expression of CG11136 in the somatic musculature. All whole embryos are shown at 200× magnification. In all views anterior is to the left, in all lateral views dorsal is at the top, B, D and E show ventral views and G shows a dorsal view.
Mentions: The expression patterns of many of the Drosophila eLRR genes identified in the bioinformatic screen were also examined in the embryo by in situ hybridisation. A summary of the expression patterns we identified and those previously described is presented [see Additional File 7]. We describe here the expression patterns of those novel eLRR genes identified in our survey that include expression in the nervous system (Figure 10). CG7702 is expressed dynamically in the peripheral nervous system (PNS), appearing at stage 11 and disappearing during stage 15. CG40500 is exclusively expressed in the CNS and is restricted to a subset of cells at the ventral midline, beginning during stage 14 and remaining into stage 17. CG11910 expression is restricted to the most dorsal layer of the CNS in a position consistent with the longitudinal glia. This expression begins at stage 12 and continues throughout embryonic development. CG5888 is expressed from stage 5 throughout the embryo with exception of the anterior tip (data not shown). At stage 15 expression of CG5888 is initiated in a subset of cells in the CNS. CG11136 is expressed in an anteroposterior stripe within the neurogenic region and in the prospective brain lobes during stages 8–10 (data not shown) and in discrete cells at the midline of the CNS during stages 11 and 12. From stage 11 onwards CG11136 expression is seen predominantly in the somatic musculature.

Bottom Line: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development.We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system.This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. jadolan@tcd.ie

ABSTRACT

Background: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships.

Results: This yields a total of 369 proteins (29 in worm, 66 in fly, 135 in mouse and 139 in human), many of them of unknown function. We group eLRR proteins into several classes: those with only LRRs, those that cluster with Toll-like receptors (Tlrs), those with immunoglobulin or fibronectin-type 3 (FN3) domains and those with some other domain. These groups show differential patterns of expansion and diversification across species. Our analyses reveal several clusters of novel genes, including two Elfn genes, encoding transmembrane proteins with eLRRs and an FN3 domain, and six genes encoding transmembrane proteins with eLRRs only (the Elron cluster). Many of these are expressed in discrete patterns in the developing mouse brain, notably in the thalamus and cortex. We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system.

Conclusion: This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.

Show MeSH
Related in: MedlinePlus