Proctolin
Encyclopedia
Proctolin is a neuropeptide
present in insect
s and crustacean
s. It was first found in Periplaneta americana, a species of cockroach
in 1975. 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.
Proctolin was the first insect neuropeptide to be sequenced. Starratt and Brown identified it as a visceral muscle
neurotransmitter. However, it now appears that there are many more functions of proctolin, and it is present in many more species.
Proctolin may also be present in molluscs, annelid
s, decapod crustacean
s, and possibly even some mammal
s.
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.
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 mammal
ian 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 neuron
al endings in adult hearts.
genome, the gene
that codes for the proctolin precursor has been identified as CG7105. The pre-proprotein is 140 amino acid
s 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 homogenate
s 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.
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
present in insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...
s and crustacean
Crustacean
Crustaceans form a very large group of arthropods, usually treated as a subphylum, which includes such familiar animals as crabs, lobsters, crayfish, shrimp, krill and barnacles. The 50,000 described species range in size from Stygotantulus stocki at , to the Japanese spider crab with a leg span...
s. It was first found in Periplaneta americana, a species of cockroach
Cockroach
Cockroaches are insects of the order Blattaria or Blattodea, of which about 30 species out of 4,500 total are associated with human habitations...
in 1975. Proctolin was extracted from 125,000 cockroaches and the Edman degradation
Edman degradation
Edman degradation, developed by Pehr Edman, is a method of sequencing amino acids in a peptide. In this method, the amino-terminal residue is labeled and cleaved from the peptide without disrupting the peptide bonds between other amino acid residues....
was carried out on the sample to determine the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
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
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
neurotransmitter. However, it now appears that there are many more functions of proctolin, and it is present in many more species.
Where proctolin is found
Proctolin is found in the following insect orders:- OrthopteraOrthopteraOrthoptera is an order of insects with paurometabolous or incomplete metamorphosis, including the grasshoppers, crickets and locusts.Many insects in this order produce sound by rubbing their wings against each other or their legs, the wings or legs containing rows of corrugated bumps...
- HemipteraHemipteraHemiptera is an order of insects most often known as the true bugs , comprising around 50,000–80,000 species of cicadas, aphids, planthoppers, leafhoppers, shield bugs, and others...
- LepidopteraLepidopteraLepidoptera is a large order of insects that includes moths and butterflies . It is one of the most widespread and widely recognizable insect orders in the world, encompassing moths and the three superfamilies of butterflies, skipper butterflies, and moth-butterflies...
- DipteraDipteraDiptera , or true flies, is the order of insects possessing only a single pair of wings on the mesothorax; the metathorax bears a pair of drumstick like structures called the halteres, the remnants of the hind wings. It is a large order, containing an estimated 240,000 species, although under half...
- HymenopteraHymenopteraHymenoptera is one of the largest orders of insects, comprising the sawflies, wasps, bees and ants. There are over 130,000 recognized species, with many more remaining to be described. The name refers to the heavy wings of the insects, and is derived from the Ancient Greek ὑμήν : membrane and...
- Coleoptera
Proctolin may also be present in molluscs, annelid
Annelid
The annelids , formally called Annelida , are a large phylum of segmented worms, with over 17,000 modern species including ragworms, earthworms and leeches...
s, decapod crustacean
Crustacean
Crustaceans form a very large group of arthropods, usually treated as a subphylum, which includes such familiar animals as crabs, lobsters, crayfish, shrimp, krill and barnacles. The 50,000 described species range in size from Stygotantulus stocki at , to the Japanese spider crab with a leg span...
s, and possibly even some mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s.
Structure
The proctolin structure is very highly conserved between species. Proctolin analogAnalog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
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
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
of proctolin is a quasi-cyclic structure with the tyrosyl side chain
Side chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called "main chain" or backbone. The placeholder R is often used as a generic placeholder for alkyl group side chains in chemical structure diagrams. To indicate other non-carbon...
pointing outwards. This is the best position for it to bind to the active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
of the receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
.
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 neurotransmitterNeurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
as in many systems where it is present it does not change the postsynaptic conductance. It is believed proctolin is a neurohormone
Neurohormone
A neurohormone is any hormone produced and released by neurons.Examples include:*Thyrotropin-releasing hormone *Gonadotropin-releasing hormone *Adrenocorticotropin-releasing hormone*Oxytocin*Antidiuretic hormone *Epinephrine...
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
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
, 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
Rhodnius prolixus
Rhodnius prolixus is the second most important triatomine vector of the Chagas parasite due to its efficient adaptation to the human domicile in northern South America, where sylvatic populations also exist, and in Central America where it is exclusively domestic...
. Another function of proctolin is that it speeds up heart rate in some insects.
A proctolin receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
in Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
has been recently identified as the orphan G-protein coupled receptor CG6986. The DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
of the gene sequence was cloned and expressed in mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian cells and the expressed receptor was specific for proctolin. In Drosophila, this receptor is strongly expressed in the head
Head
In anatomy, the head of an animal is the rostral part that usually comprises the brain, eyes, ears, nose and mouth . Some very simple animals may not have a head, but many bilaterally symmetric forms do....
, the larval hindgut
Hindgut
The hindgut is the posterior part of the alimentary canal. In mammals, it includes the distal third of the transverse colon and the splenic flexure, the descending colon, sigmoid colon and rectum.-Blood flow:...
, the aorta
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
and on neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
al endings in adult hearts.
Synthesis and breakdown
Through analysis of the Drosophila melanogasterDrosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
genome, the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
that codes for the proctolin precursor has been identified as CG7105. The pre-proprotein is 140 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s 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 homogenate
Homogenization (biology)
Homogenization is a process that involves breaking apart cells — releasing organelles and cytoplasm.When the purpose is to extract organelles, it is frequently done in two steps; first using a blender to break the tissue up, and then with an ultrasonic or mechanical tissue disruptor. The...
s from Periplaneta americana a soluble aminopeptidase
Aminopeptidase
Aminopeptidase is a zinc-dependent enzyme produced and secreted by glands of the small intestine. It helps the enzymatic digestion of proteins. Additional digestive enzymes produced by these glands include dipeptidases, maltase, sucrase, lactase, and enterokinase.Aminopeptidases catalyze the...
as a key enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that degrades proctolin was identified. Another enzyme was also identified that cleaves the Tyr-Leu bond.