Disease relevance of Proct

• Two genes in Drosophila, rdgA and rdgB, which when defective cause retinal degeneration, were discovered by Hotta and Benzer (Hotta, Y., and S. Benzer. 1970. Proc. Natl, Acad. Sci. U. S, A. 67:1156-1163) [1].

Psychiatry related information on Proct

• In D. melanogaster, three allelic per mutations have been isolated which affect the periodicity of the circadian oscillators affecting both eclosion and locomotor activity [Konopka, R. & Benzer S. (1971) Proc. Natl. Acad. Sci. USA 68, 2112-2116] [2].
• Drosophila carrying the X-linked mutation dunce (dnc) showed poor learning in a negative reinforcement olfactory conditioning paradigm (Dudai, Y., Y.-N. Jan, D. Byers, W.G. Quinn, and S. Benzer (1976) Proc. Natl. Acad. Sci. U.S.A. 73: 1684-1688) [3].

High impact information on Proct

• We show that the Mhc1 mutation is essentially a null allele which results in the dominant-flightless and recessive-lethal phenotypes associated with this mutant (Mogami, K., P. T. O'Donnell, S. I. Bernstein, T. R. F. Wright, C. P. Emerson, Jr. 1986. Proc. Natl. Acad. Sci. USA. 83:1393-1397) [4].
• In competition-based studies, the CG6986 receptor binds proctolin with high affinity (IC(50) = 4 nM) [5].
• Proctolin is a bioactive neuropeptide that modulates interneuronal and neuromuscular synaptic transmission in a wide variety of arthropods [5].
• This is a 16-bp deletion in the 5' region of a desaturase gene (desat2) that was recently suggested to be responsible for the CH polymorphism on the basis of its expression [Dallerac, R., Labeur, C., Jallon, J.-M., Knipple, D. C., Roelofs, W. L. & Wicker-Thomas, C. (2000) Proc. Natl. Acad. Sci. 97, 9449--9454] [6].
• Waters and colleagues recently suggested [Waters, L. C., Zelhof, A. C., Shaw, B. J. & Ch'ang, L.-Y. (1992) Proc. Natl. Acad. Sci. USA 89, 4855-4859] that an insertion of a long terminal repeat of transposable element 17.6 into the 3' untranslated region of a P450 gene leads to susceptibility to the insecticide DDT in Drosophila melanogaster [7].

Biological context of Proct

• In addition, low concentration of the specific DPP III inhibitor tynorphin prevented proctolin degradation (IC50 = 0.62 +/- 0.15 micro m) [8].
• Northern blots showed that the Drosophila proctolin receptor was only weakly expressed in embryos, larvae, pupae, and in the thoraces and abdomina of adult flies, but strongly in the heads of adult animals [9].
• To account for the transmission of mitochondrial DNA between conspecific species Drosophila pseudoobscura and D. persimilis in sympatry reported by J.R. Powell [Powell, J.R. (1983) Proc. Natl. Acad. Sci. USA 80, 492-495], a simple model of gene flow and selection in infinite populations is analyzed [10].
• When expressed in mammalian cells, CG6986 confers second messenger activation after proctolin application, with an EC(50) of 0.3 nM [5].
• The catalytic activity of topoisomerase II is stimulated approximately 2-3-fold following phosphorylation by casein kinase II (Ackerman, P., Glover, C. V. C., and Osheroff, N. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 3164-3168) [11].

Anatomical context of Proct

• Two proctolin-binding proteins solubilized from 1600 cockroach hindgut membranes were purified 1000-fold using five chromatography steps [12].
• Finally, anti-(DPP III) immunoreactivity was observed in the central nervous system of D. melanogaster larva, supporting a functional role for DPP III in proctolin degradation [13].
• In this report, we have disrupted all somatic copies of the Tetrahymena HHP1 gene, which encodes an HP1-like protein, Hhp1p, in macronuclei (H. Huang, E. A. Wiley, R. C. Lending, and C. D. Allis, Proc. Natl. Acad. Sci. USA 95:13624-13629, 1998) [14].
• We have previously identified an exceptional mRNA that appears to be depleted from early-embryo polysomes [Fruscoloni, P., Al-Atia, G. R., & Jacobs-Lorena, M. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 3359-3363] [15].
• The distribution of proctolin suggests roles as a neuromodulator in motoneurons and interneurons, and as a neurohormone that could be released from brain neurosecretory cells with terminations in the ring gland [16].

Associations of Proct with chemical compounds

• The purified proteins removed the N-terminal dipeptide from the insect myotropic neuropeptide proctolin (Arg-Tyr-Leu-Pro-Thr) with a Km value of 3.8 +/- 1.1 microM [12].
• Substance P and proctolin were found in seven and eight out of ten clones, respectively [17].
• It has been proposed that uric acid is an important scavenger of deleterious oxygen radicals in biological systems [Ames, B. N., Cathcart, R., Schwiers, E. & Hochstein, P. (1981) Proc. Natl. Acad. Sci. USA 78, 6858-6852] [18].
• This system was chosen because of the previous investigations [Dion, A.S. & Herbst, E.J. (1967) Proc. Natl. Acad. Sci. U.S.A. 58, 2367-2371; Herbst, E.J. & Dion, A.S. (1970) Fed. Proc. Fed. Am. Soc. Exp. Biol. 29, 1563-1567] relating putrescine and spermidine to growth and development of Drosophila [19].
• The neurons express several synaptic cotransmitters, including glutamate, proctolin, and octopamine, and are specialized by their synaptic morphology, neurotransmitters, and connectivity [20].

Regulatory relationships of Proct

• These results constitute the first characterization of an evolutionarily conserved insect DPP III that is expressed as a cytosolic and a membrane peptidase involved in proctolin degradation [8].

Analytical, diagnostic and therapeutic context of Proct

• Proctolin was recovered from the CNS, hindgut, and segmental bodywall using reverse-phase HPLC, and characterized by bioassay, immunoassay, and enzymatic analysis [21].
• A recent study using the polymerase chain reaction (PCR) identified six new candidate Klps in Drosophila, making the total number of members of this family in Drosophila at least 11 (Stewart et al., 1991, Proc. Natl. Acad. Sci. USA 88, 4424-4427) [22].
• In situ hybridization with a riboprobe to the Proct gene revealed a distribution of transcript in neurons of the larval central nervous system (CNS) matching that seen with antiserum to proctolin [16].

References