High impact information on Ca-P60A

• We identified a lethal complementation group recovered in a screen for mutations that reduce Notch activity as loss-of-function alleles of the Drosophila Ca(2+)-ATPase gene Ca-P60A [1].
• Notch and several other transmembrane proteins are mislocalized in tissue clones homozygous for Ca-P60A mutations, demonstrating a general effect on membrane protein trafficking caused by a deficiency in Ca(2+)-ATPase [1].
• Analysis of Ca-P60A mutants indicates that Ca(2+)-ATPase is essential for cell viability and tissue morphogenesis during development [1].
• Maximum parsimony and Neighbour Joining were used to generate a phylogenetic classification of Drosophila ryanodine and insitol triphosphate receptors and Ca2+-ATPase based on 48 invertebrate and vertebrate complete sequences [2].
• Despite evolutionary distances, our functional results demonstrate that Drosophila ryanodine and inositol triphosphate receptors and Ca2+-ATPase are reasonably similar to vertebrate counterparts [2].

Biological context of Ca-P60A

• Conditional paralysis of SERCA mutants is also marked by prolonged neural activity-driven muscle contraction, thus reflecting the phylogenetically conserved role of SERCA in terminating contraction [3].
• Patterns of gene expression for SERCA and other sarcomeric proteins during the crustacean moulting cycle may be regulated by ecdysteroids and/or mechanical stimulation [4].
• SERCA was most abundant in muscle (axial abdominal, cardiac and stomach), where it is involved in Ca(2+) resequestration during relaxation, and in eggs, where it may be implicated in early embryogenesis [4].
• We describe the cloning, sequencing and characterization of a novel SERCA cDNA (3856 bp) obtained from crayfish axial abdominal muscle by reverse transcription/polymerase chain reaction (RT-PCR) followed by rapid amplification of cDNA ends (RACE) [4].
• Conditional mutations in SERCA, the Sarco-endoplasmic reticulum Ca(2+)-ATPase, alter heart rate and rhythmicity in Drosophila [5].

Anatomical context of Ca-P60A

• SERCA, a sarco-endoplasmic reticulum calcium ATPase, being the main agent for calcium uptake into the ER, plays a central role in this process [3].
• In Ca2+-free medium, the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, elevates [Ca2+]i only in the smaller stellate cells, suggesting that principal cells do not contain a thapsigargin-sensitive intracellular pool [6].
• Following the sarcoplasmic reticulum (SR) Ca(2+) store depletion by thapsigargin (Tg), a SERCA inhibitor, OAG and PHE were both still able to activate Ca(2+) influx [7].
• A combination of RNAi and calcium imaging has provided a direct demonstration of key roles for the Ins(1,4,5)P(3)R and the SERCA pump in the response to DM1 receptor activation.Thus, we show that silencing of individual genes by RNAi in a well characterised Drosophila S2 cell line offers experimental opportunities for cell-signalling studies [8].
• Like its relative in Drosophila, TRPC1 looks likely to function in a signalplex, a protein complex including inositol 1,4,5-triphosphate (IP(3)) receptor, plasma membrane calcium-ATPase, caveolin-1 and calmodulin [9].

Associations of Ca-P60A with chemical compounds

• We have shown that RNAi knock down of either the inositol 1,4,5-trisphosphate receptor (Ins(1,4,5)P(3)R), or the SERCA calcium pump in the S2-DM1 cells blocks the increase in intracellular calcium concentration ([Ca(2+)](i)) resulting from activation of the DM1 receptor by 100 microM carbamylcholine (CCh) [8].

Other interactions of Ca-P60A

• Analysis of conditional paralytic mutants in Drosophila sarco-endoplasmic reticulum calcium ATPase reveals novel mechanisms for regulating membrane excitability [3].
• Bursts of neural activity induced in Drosophila comatosets and CaP60A Kumts mutants, with conditional defects in N-ethylmaleimide-sensitive fusion factor 1 and sarco-endoplasmic reticulum Ca2+ ATPase, respectively, result in persistent (>4 hr) activation of neuronal extracellular signal-regulated kinase (ERK) [10].

Analytical, diagnostic and therapeutic context of Ca-P60A

• Confocal microscopy demonstrated abundant expression of ryanodine and inositol triphosphate receptors and abundant Ca2+-ATPase in Drosophila embryos and adults [2].
• The RT PCR approach was used to obtain the nucleotide sequence of the mRNA of a sarco/endoplasmic reticulum calcium transporting ATPase (SERCA) from the cross-striated (phasic) part of the adductor muscle of the deep sea scallop [11].

References