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Drosophila Ana2 is a conserved centriole duplication factor.

Stevens NR, Dobbelaere J, Brunk K, Franz A, Raff JW - J. Cell Biol. (2010)

Bottom Line: Functional orthologues of all but SAS-5 have been found in other species.Asl is now known to be essential for centriole duplication in flies, but no equivalent protein has been found in worms.We propose that members of the SAS-5/Ana2/STIL family of proteins are key conserved components of the centriole duplication machinery.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Gurdon Institute, Cambridge, England CB2 1QN, UK.

ABSTRACT
In Caenorhabditis elegans, five proteins are required for centriole duplication: SPD-2, ZYG-1, SAS-5, SAS-6, and SAS-4. Functional orthologues of all but SAS-5 have been found in other species. In Drosophila melanogaster and humans, Sak/Plk4, DSas-6/hSas-6, and DSas-4/CPAP-orthologues of ZYG-1, SAS-6, and SAS-4, respectively-are required for centriole duplication. Strikingly, all three fly proteins can induce the de novo formation of centriole-like structures when overexpressed in unfertilized eggs. Here, we find that of eight candidate duplication factors identified in cultured fly cells, only two, Ana2 and Asterless (Asl), share this ability. Asl is now known to be essential for centriole duplication in flies, but no equivalent protein has been found in worms. We show that Ana2 is the likely functional orthologue of SAS-5 and that it is also related to the vertebrate STIL/SIL protein family that has been linked to microcephaly in humans. We propose that members of the SAS-5/Ana2/STIL family of proteins are key conserved components of the centriole duplication machinery.

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Ana2 is related to vertebrate STIL. Schematic of human STIL Drosophila Ana2, and C. elegans SAS-5. All three proteins have a central, coiled-coil domain (green) and a conserved region near the C terminus (blue): the STAN motif. An alignment of the STAN motif is shown in full, with an alignment including SAS-5 below. Both are colored according to the Blosum62 coloring scheme, where dark blue indicates a match to the consensus sequence and light blue indicates a positive Blosum62 score. Asterisks indicate residues are identical in all aligned sequences, colons indicate conserved substitutions, and periods indicate semiconserved substitutions.
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fig5: Ana2 is related to vertebrate STIL. Schematic of human STIL Drosophila Ana2, and C. elegans SAS-5. All three proteins have a central, coiled-coil domain (green) and a conserved region near the C terminus (blue): the STAN motif. An alignment of the STAN motif is shown in full, with an alignment including SAS-5 below. Both are colored according to the Blosum62 coloring scheme, where dark blue indicates a match to the consensus sequence and light blue indicates a positive Blosum62 score. Asterisks indicate residues are identical in all aligned sequences, colons indicate conserved substitutions, and periods indicate semiconserved substitutions.

Mentions: Having shown that Ana2 is the likely SAS-5 functional orthologue in Drosophila, we looked for Ana2/SAS-5 orthologues in other species. Using an iterative basic local alignment search tool (BLAST) search, we found significant homology between Ana2 and the STIL or SIL protein family. Moreover, the reciprocal iterative BLAST search starting with zebrafish STIL identified Ana2 as the most similar Drosophila protein. Although vertebrate STIL family members are larger than Ana2 or SAS-5, all of these proteins share a short, central, coiled-coil domain (Fig. 5). In addition, we identified a particularly conserved region of ∼90 aa toward the C terminus of Ana2 and STIL, which we called the STil/ANa2 (STAN) motif. The STAN motif of Ana2 is 31% identical (48% similar) to that of zebrafish STIL. A divergent STAN motif can be detected in SAS-5, which is 12% identical (26% similar) to that of zebrafish STIL (Fig. 5). Importantly, the STAN motif is within the regions of SAS-5 and Ana2 that interact with SAS-6 and DSas-6, respectively (Fig. 4 F; Boxem et al., 2008).


Drosophila Ana2 is a conserved centriole duplication factor.

Stevens NR, Dobbelaere J, Brunk K, Franz A, Raff JW - J. Cell Biol. (2010)

Ana2 is related to vertebrate STIL. Schematic of human STIL Drosophila Ana2, and C. elegans SAS-5. All three proteins have a central, coiled-coil domain (green) and a conserved region near the C terminus (blue): the STAN motif. An alignment of the STAN motif is shown in full, with an alignment including SAS-5 below. Both are colored according to the Blosum62 coloring scheme, where dark blue indicates a match to the consensus sequence and light blue indicates a positive Blosum62 score. Asterisks indicate residues are identical in all aligned sequences, colons indicate conserved substitutions, and periods indicate semiconserved substitutions.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2819680&req=5

fig5: Ana2 is related to vertebrate STIL. Schematic of human STIL Drosophila Ana2, and C. elegans SAS-5. All three proteins have a central, coiled-coil domain (green) and a conserved region near the C terminus (blue): the STAN motif. An alignment of the STAN motif is shown in full, with an alignment including SAS-5 below. Both are colored according to the Blosum62 coloring scheme, where dark blue indicates a match to the consensus sequence and light blue indicates a positive Blosum62 score. Asterisks indicate residues are identical in all aligned sequences, colons indicate conserved substitutions, and periods indicate semiconserved substitutions.
Mentions: Having shown that Ana2 is the likely SAS-5 functional orthologue in Drosophila, we looked for Ana2/SAS-5 orthologues in other species. Using an iterative basic local alignment search tool (BLAST) search, we found significant homology between Ana2 and the STIL or SIL protein family. Moreover, the reciprocal iterative BLAST search starting with zebrafish STIL identified Ana2 as the most similar Drosophila protein. Although vertebrate STIL family members are larger than Ana2 or SAS-5, all of these proteins share a short, central, coiled-coil domain (Fig. 5). In addition, we identified a particularly conserved region of ∼90 aa toward the C terminus of Ana2 and STIL, which we called the STil/ANa2 (STAN) motif. The STAN motif of Ana2 is 31% identical (48% similar) to that of zebrafish STIL. A divergent STAN motif can be detected in SAS-5, which is 12% identical (26% similar) to that of zebrafish STIL (Fig. 5). Importantly, the STAN motif is within the regions of SAS-5 and Ana2 that interact with SAS-6 and DSas-6, respectively (Fig. 4 F; Boxem et al., 2008).

Bottom Line: Functional orthologues of all but SAS-5 have been found in other species.Asl is now known to be essential for centriole duplication in flies, but no equivalent protein has been found in worms.We propose that members of the SAS-5/Ana2/STIL family of proteins are key conserved components of the centriole duplication machinery.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Gurdon Institute, Cambridge, England CB2 1QN, UK.

ABSTRACT
In Caenorhabditis elegans, five proteins are required for centriole duplication: SPD-2, ZYG-1, SAS-5, SAS-6, and SAS-4. Functional orthologues of all but SAS-5 have been found in other species. In Drosophila melanogaster and humans, Sak/Plk4, DSas-6/hSas-6, and DSas-4/CPAP-orthologues of ZYG-1, SAS-6, and SAS-4, respectively-are required for centriole duplication. Strikingly, all three fly proteins can induce the de novo formation of centriole-like structures when overexpressed in unfertilized eggs. Here, we find that of eight candidate duplication factors identified in cultured fly cells, only two, Ana2 and Asterless (Asl), share this ability. Asl is now known to be essential for centriole duplication in flies, but no equivalent protein has been found in worms. We show that Ana2 is the likely functional orthologue of SAS-5 and that it is also related to the vertebrate STIL/SIL protein family that has been linked to microcephaly in humans. We propose that members of the SAS-5/Ana2/STIL family of proteins are key conserved components of the centriole duplication machinery.

Show MeSH
Related in: MedlinePlus