Proctolin is a

neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like th ...

present in

insect Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body (head, thorax and abdomen), three pairs ...

s and

crustacean Crustaceans (Crustacea, ) form a large, diverse arthropod taxon which includes such animals as decapods, seed shrimp, branchiopods, fish lice, krill, remipedes, isopods, barnacles, copepods, amphipods and mantis shrimp. The crustacean gro ...

s. It was first found in '' Periplaneta americana'', a species of

cockroach Cockroaches (or roaches) are a Paraphyly, paraphyletic group of insects belonging to Blattodea, containing all members of the group except termites. About 30 cockroach species out of 4,600 are associated with human habitats. Some species are we ...

in 1975. Proctolin was extracted from 125,000 cockroaches and the Edman degradation was carried out on the sample to determine the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

sequence, which is Arg-Tyr-Leu-Pro-Thr. Proctolin was the first insect neuropeptide to be sequenced. Starratt and Brown identified it as a visceral

muscle Skeletal muscles (commonly referred to as muscles) are Organ (biology), organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other ...

neurotransmitter. However, it now appears that there are many more functions of proctolin, and it is present in many more species.

Localisation

Proctolin is found in the following insect orders: *

Orthoptera Orthoptera () is an order of insects that comprises the grasshoppers, locusts, and crickets, including closely related insects, such as the bush crickets or katydids and wētā. The order is subdivided into two suborders: Caelifera – grass ...

* Hemiptera * Diptera *

Coleoptera Beetles are insects that form the order Coleoptera (), in the superorder Endopterygota. Their front pair of wings are hardened into wing-cases, elytra, distinguishing them from most other insects. The Coleoptera, with about 400,000 describ ...

Proctolin may also be present in molluscs,

annelid The annelids (Annelida , from Latin ', "little ring"), also known as the 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 ecol ...

s, decapod

s, and possibly even some mammals.

Structure

The proctolin structure is very highly conserved between species. Proctolin

analog Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analo ...

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

insecticides Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed t ...

Function

Proctolin is not considered a classical

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neur ...

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 In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses fr ...

, using proctolin as a

cotransmitter Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron) ...

, often with a more common neurotransmitter such as

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

. 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 ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or " pomace fly". Starting with ...

'' 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 A head is the part of an organism which usually includes the ears, brain, forehead, cheeks, chin, eyes, nose, and mouth, each of which aid in various sensory functions such as sight, hearing, smell, and taste. Some very simple animals may no ...

, the larval hindgut, the

aorta The aorta ( ) is the main and largest artery in the human body, originating from the left ventricle of the heart and extending down to the abdomen, where it splits into two smaller arteries (the common iliac arteries). The aorta distributes ...

and on

neuron A neuron, neurone, or nerve cell is an membrane potential#Cell excitability, electrically excitable cell (biology), cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous ...

al endings in adult hearts.

Synthesis and breakdown

Through analysis of the ''

'' genome, the

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

that codes for the proctolin precursor has been identified as CG7105. The pre-proprotein is 140

s long and has cleavage sites either side of the RYLPT proctolin sequence. It is thought a signal

peptidase A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

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 Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

that degrades proctolin was identified. Another enzyme was also identified that cleaves the Tyr-Leu bond.

References

* * {{cite journal , vauthors=Orchard I, Belanger JH, Lange AB , title=Proctolin: a review with emphasis on insects , journal=J. Neurobiol. , volume=20 , issue=5 , pages=470–96 , year=1989 , pmid=2568390 , doi=10.1002/neu.480200515 Neuropeptides Pentapeptides