Proctolin

Last updated May 03, 2019

Proctolin is a neuropeptide present in insects and crustaceans. It was first found in Periplaneta americana , a species of cockroach in 1975.^[1] Proctolin was extracted from 125,000 cockroaches and the Edman degradation was carried out on the sample to determine the amino acid sequence, which is Arg-Tyr-Leu-Pro-Thr.

Neuropeptides are small protein-like molecules (peptides) used by neurons to communicate with each other. They are neuronal signalling molecules that influence the activity of the brain and the body in specific ways. Different neuropeptides are involved in a wide range of brain functions, including analgesia, reward, food intake, metabolism, reproduction, social behaviors, learning and memory.

Insects or Insecta are hexapod invertebrates and the largest group within the arthropod phylum. Definitions and circumscriptions vary; usually, insects comprise a class within the Arthropoda. As used here, the term Insecta is synonymous with Ectognatha. Insects have a chitinous exoskeleton, a three-part body, three pairs of jointed legs, compound eyes and one pair of antennae. Insects are the most diverse group of animals; they include more than a million described species and represent more than half of all known living organisms. The total number of extant species is estimated at between six and ten million; potentially over 90% of the animal life forms on Earth are insects. Insects may be found in nearly all environments, although only a small number of species reside in the oceans, which are dominated by another arthropod group, crustaceans.

Crustaceans form a large, diverse arthropod taxon which includes such familiar animals as crabs, lobsters, crayfish, shrimps, prawns, krill, woodlice, and barnacles. The crustacean group is usually treated as a subphylum, and because of recent molecular studies it is now well accepted that the crustacean group is paraphyletic, and comprises all animals in the Pancrustacea clade other than hexapods. Some crustaceans are more closely related to insects and other hexapods than they are to certain other crustaceans.

Muscle is a soft tissue found in most animals. Muscle cells contain protein filaments of actin and myosin that slide past one another, producing a contraction that changes both the length and the shape of the cell. Muscles function to produce force and motion. They are primarily responsible for maintaining and changing posture, locomotion, as well as movement of internal organs, such as the contraction of the heart and the movement of food through the digestive system via peristalsis.

Localisation

Proctolin is found in the following insect orders:

Orthoptera is an order of insects that comprises the grasshoppers, locusts and crickets, including closely related insects such as the katydids and wetas. The order is subdivided into two suborders: Caelifera – grasshoppers, locusts and close relatives; and Ensifera – crickets and close relatives.

The Hemiptera or true bugs are an order of insects comprising some 50,000 to 80,000 species of groups such as the cicadas, aphids, planthoppers, leafhoppers, and shield bugs. They range in size from 1 mm (0.04 in) to around 15 cm (6 in), and share a common arrangement of sucking mouthparts. The name "true bugs" is sometimes limited to the suborder Heteroptera. Many insects commonly known as "bugs" belong to other orders; for example, the lovebug is a fly, while the May bug and ladybug are beetles.

Lepidoptera is an order of insects that includes butterflies and moths. About 180,000 species of the Lepidoptera are described, in 126 families and 46 superfamilies, 10 per cent of the total described species of living organisms. It is one of the most widespread and widely recognizable insect orders in the world. The Lepidoptera show many variations of the basic body structure that have evolved to gain advantages in lifestyle and distribution. Recent estimates suggest the order may have more species than earlier thought, and is among the four most speciose orders, along with the Hymenoptera, Diptera, and Coleoptera.

Proctolin may also be present in molluscs, annelids, decapod crustaceans, and possibly even some mammals.

The annelids, also known as the ringed worms or segmented worms, are a large phylum, with over 22,000 extant species including ragworms, earthworms, and leeches. The species exist in and have adapted to various ecologies – some in marine environments as distinct as tidal zones and hydrothermal vents, others in fresh water, and yet others in moist terrestrial environments.

Mammals are vertebrate animals constituting the class Mammalia, and characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex, fur or hair, and three middle ear bones. These characteristics distinguish them from reptiles and birds, from which they diverged in the late Triassic, 201–227 million years ago. There are around 5,450 species of mammals. The largest orders are the rodents, bats and Soricomorpha. The next three are the Primates, the Cetartiodactyla, and the Carnivora.

Structure

The proctolin structure is very highly conserved between species. Proctolin analogs have been synthesised in order to find out more about the structure of the molecule. It was found that each amino acid in the proctolin molecule was needed for full activity. The preferred conformation of proctolin is a quasi-cyclic structure with the tyrosyl side chain pointing outwards. This is the best position for it to bind to the active site of the receptor.

A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together, and can be represented using structural formulae and by molecular models; complete electronic structure descriptions include specifying the occupation of a molecule's molecular orbitals. Structure determination can be applied to a range of targets from very simple molecules, to very complex ones.

In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a larger hydrocarbon backbone. It is one factor in determining a molecule's properties and reactivity. A side chain is also known as a pendant chain, but a pendant group has a different definition.

In biology, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of residues that form temporary bonds with the substrate and residues that catalyse a reaction of that substrate. Although the active site is small relative to the whole volume of the enzyme, it is the most important part of the enzyme as it directly catalyzes the chemical reaction. It usually consists of three to four amino acids, while other amino acids within the protein are required to maintain the protein tertiary structure of the enzyme.

A large range of proctolin peptide and nonpeptide mimetics have been synthesised to try and produce new effective insecticides.

Function

Proctolin is not considered a classical neurotransmitter as in many systems where it is present it does not change the postsynaptic conductance. It is believed proctolin is a neurohormone in crustaceans and in some insects. More frequently, proctolin is referred to as a neuromodulator. This is because all proctolinergic systems change the way impulses are transmitted across a synapse, using proctolin as a cotransmitter, often with a more common neurotransmitter such as glutamate.

Proctolin is a potent stimulator in the contraction of a number of visceral and skeletal muscles in insects. Proctolin stimulates contractions of the hindgut in P. americana, the foregut in S. gregaria and the midgut of Diploptera punctata and L. migratoria. Proctolin also modulates reproductive tissue, stimulating contractions of the oviducts in P. americana, Leucophaea maderae, L. migratoria, and spermathecae in L. migratoria and Rhodnius prolixus . Another function of proctolin is that it speeds up heart rate in some insects.

A proctolin receptor in Drosophila melanogaster has been recently identified as the orphan G-protein coupled receptor CG6986. The DNA of the gene sequence was cloned and expressed in mammalian cells and the expressed receptor was specific for proctolin. In Drosophila, this receptor is strongly expressed in the head, the larval hindgut, the aorta and on neuronal endings in adult hearts.

Synthesis and breakdown

Through analysis of the Drosophila melanogaster genome, the gene that codes for the proctolin precursor has been identified as CG7105. The pre-proprotein is 140 amino acids long and has cleavage sites either side of the RYLPT proctolin sequence. It is thought a signal peptidase cuts at these cleavage sites to produce the proctolin peptide.

Proctolin needs to be broken down to stop it staying permanently bound to the receptor. This is done by peptidases. The first step of breakdown is cleavage of the Arg-Tyr bond, followed by the cleavage of the Tyr-Leu bond. Using a number of tissue homogenates from Periplaneta americana a soluble aminopeptidase as a key enzyme that degrades proctolin was identified. Another enzyme was also identified that cleaves the Tyr-Leu bond.

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References

Kastin, Abba J. (2006). Handbook of Biologically Active Peptides. Boston: Academic Press. ISBN 0-12-369442-6.
Orchard I, Belanger JH, Lange AB (1989). "Proctolin: a review with emphasis on insects". J. Neurobiol. 20 (5): 470–96. doi:10.1002/neu.480200515. PMID 2568390.

↑ Starratt AN, Brown BE (1975). "Structure of the pentapeptide proctolin, a proposed neurotransmitter in insects". Life Sci. 17 (8): 1253–6. doi:10.1016/0024-3205(75)90134-4. PMID 576.

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[1] Starratt AN, Brown BE (1975). "Structure of the pentapeptide proctolin, a proposed neurotransmitter in insects". Life Sci. 17 (8): 1253–6. doi:10.1016/0024-3205(75)90134-4. PMID 576.