TY - JOUR
T1 - Comparative genomic and phylogenetic analyses of calcium ATPases and calcium-regulated proteins in the Apicomplexa
AU - Nagamune, Kisaburo
AU - Sibley, L. David
PY - 2006/8
Y1 - 2006/8
N2 - The phylum Apicomplexa comprises a large group of early branching eukaryotes that includes a number of human and animal parasites. Calcium controls a number of vital processes in apicomplexans including protein secretion, motility, and differentiation. Despite the importance of calcium as a second messenger, very little is known about the systems that control homeostasis or that regulate calcium signaling in parasites. The recent completion of many apicomplexan genomes provides new opportunity to define calcium response pathways in this group of parasites in comparison to model organisms. Whole-genome comparison between the apicomplexans Plasmodium spp., Cryptosporidium spp., and Toxoplasma gondii revealed the presence of several P-Type Ca 2+ transporting ATPases including a single endoplasmic reticulum (ER)-type sarcoplasmic-endoplasmic reticulum Ca 2+ ATPase, several Golgi-like Ca 2+ ATPases, and a single Ca 2+/H + exchanger. Only T. gondii showed evidence of plasma membrane-type Ca 2+ ATPases or voltage-gated calcium channels. Despite pharmacological evidence for IP 3 and ryanodine-mediated calcium release, animal-type calcium channels were not readily identified in parasites, indicating they are more similar to plants. Downstream of calcium release, a variety of EF-hand-containing proteins regulate calcium responses. Our analyses detected a single conserved calmodulin (CaM) homologue, 3 distinct centrin (CETN)-caltractin-like proteins, one of which is shared with ciliates, and a variety of deep-branching, CaM-CETN-like proteins. Apicomplexans were also found to contain a wide array of calcium-dependent protein kinases (CDPKs), which are commonly found in plants. Toxoplasma gondii contains more than 20 CDPK or CDPK-related kinases, which likely regulate a variety of responses including secretion, motility, and differentiation. Genomic and phylogenetic comparisons revealed that apicomplexans contain a variety of unusual calcium response pathways that are distinct from those seen in vertebrates. Notably, plant-like pathways for calcium release channels and calcium-dependent kinases are found in apicomplexans. The experimental flexibility of T. gondii should allow direct experimental manipulation of these pathways to validate their biological roles. The central importance of calcium in signaling and development, and the novel characteristics of many of these systems, indicates that parasite calcium pathways may be exploited as new therapeutic targets for intervention.
AB - The phylum Apicomplexa comprises a large group of early branching eukaryotes that includes a number of human and animal parasites. Calcium controls a number of vital processes in apicomplexans including protein secretion, motility, and differentiation. Despite the importance of calcium as a second messenger, very little is known about the systems that control homeostasis or that regulate calcium signaling in parasites. The recent completion of many apicomplexan genomes provides new opportunity to define calcium response pathways in this group of parasites in comparison to model organisms. Whole-genome comparison between the apicomplexans Plasmodium spp., Cryptosporidium spp., and Toxoplasma gondii revealed the presence of several P-Type Ca 2+ transporting ATPases including a single endoplasmic reticulum (ER)-type sarcoplasmic-endoplasmic reticulum Ca 2+ ATPase, several Golgi-like Ca 2+ ATPases, and a single Ca 2+/H + exchanger. Only T. gondii showed evidence of plasma membrane-type Ca 2+ ATPases or voltage-gated calcium channels. Despite pharmacological evidence for IP 3 and ryanodine-mediated calcium release, animal-type calcium channels were not readily identified in parasites, indicating they are more similar to plants. Downstream of calcium release, a variety of EF-hand-containing proteins regulate calcium responses. Our analyses detected a single conserved calmodulin (CaM) homologue, 3 distinct centrin (CETN)-caltractin-like proteins, one of which is shared with ciliates, and a variety of deep-branching, CaM-CETN-like proteins. Apicomplexans were also found to contain a wide array of calcium-dependent protein kinases (CDPKs), which are commonly found in plants. Toxoplasma gondii contains more than 20 CDPK or CDPK-related kinases, which likely regulate a variety of responses including secretion, motility, and differentiation. Genomic and phylogenetic comparisons revealed that apicomplexans contain a variety of unusual calcium response pathways that are distinct from those seen in vertebrates. Notably, plant-like pathways for calcium release channels and calcium-dependent kinases are found in apicomplexans. The experimental flexibility of T. gondii should allow direct experimental manipulation of these pathways to validate their biological roles. The central importance of calcium in signaling and development, and the novel characteristics of many of these systems, indicates that parasite calcium pathways may be exploited as new therapeutic targets for intervention.
KW - Apicomplexan
KW - Calcium
KW - Calmodulin
KW - Centrin
KW - EF-hand
KW - Kinase
UR - http://www.scopus.com/inward/record.url?scp=33748079101&partnerID=8YFLogxK
U2 - 10.1093/molbev/msl026
DO - 10.1093/molbev/msl026
M3 - Article
C2 - 16751258
AN - SCOPUS:33748079101
SN - 0737-4038
VL - 23
SP - 1613
EP - 1627
JO - Molecular biology and evolution
JF - Molecular biology and evolution
IS - 8
ER -