Neuronal calcium sensor-1
Encyclopedia
Neuronal calcium sensor-1 (NCS-1) also known as frequenin homolog (Drosophila) (freq) is a protein
that in humans is encoded by the FREQ gene
. This protein regulates G protein-coupled receptor
phosphorylation
in a calcium-dependent manner and can substitute for calmodulin
.
NCS-1 is a member of neuronal calcium sensor
family which, are EF hand
containing calcium-myristoyl-switch proteins
. This calcium binding protein was originally discovered in Drosophila melanogaster
and named Frequenin (Frq). Drosophila null frq mutants have impaired neurotransmitter release and enhanced nerve terminal growth. NCS-1 has a known role in learning
and memory
in C. elegans
and mammals. NCS-1 is a calcium sensor, not a calcium buffer (chelator); thus it is a high-affinity, low-capacity, calcium-binding protein.
as a mutation associated with calcium stimulated increases in neurotransmission
. Later work in bovine chromaffin cell
s confirmed NCS-1 as a modulator of neurotransmission. The designation 'NCS-1' came from the assumption that the protein was expressed only in neuronal cell types, which is not the case.
and some forms of schizophrenia
and decreases in inflammatory bowel disease
. NCS-1 has also been linked with Autism: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866544/?tool=pubmed.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the FREQ 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...
. This protein regulates G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
in a calcium-dependent manner and can substitute for calmodulin
Calmodulin
Calmodulin is a calcium-binding protein expressed in all eukaryotic cells...
.
NCS-1 is a member of neuronal calcium sensor
Neuronal calcium sensor
Neuronal Calcium Sensor is a large family of proteins which work as calcium dependent molecular switches and includes members like Frequenin , recoverin, GCAP, neurocalcin, visinin etc...
family which, are EF hand
EF hand
The EF hand is a helix-loop-helix structural domain found in a large family of calcium-binding proteins. The EF-hand motif contains a helix-loop-helix topology, much like the spread thumb and forefinger of the human hand, in which the Ca2+ ions are coordinated by ligands within the loop...
containing calcium-myristoyl-switch proteins
. This calcium binding protein was originally discovered 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...
and named Frequenin (Frq). Drosophila null frq mutants have impaired neurotransmitter release and enhanced nerve terminal growth. NCS-1 has a known role in learning
Learning
Learning is acquiring new or modifying existing knowledge, behaviors, skills, values, or preferences and may involve synthesizing different types of information. The ability to learn is possessed by humans, animals and some machines. Progress over time tends to follow learning curves.Human learning...
and memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
in C. elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
and mammals. NCS-1 is a calcium sensor, not a calcium buffer (chelator); thus it is a high-affinity, low-capacity, calcium-binding protein.
Function
Frq can substitute for calmodulin in some situations. It is thought to be associated with neuronal secretory vesicles and regulate neurosecretion.- It is the Ca2+-sensing subunit of the yeast phosphatidylinositol (PtdIns)-4-OH kinase, PIK1
- It binds to many proteins, some in calcium dependent and some in calcium independent ways, and switches many of the targets "on" (some off).
- CalcineurinCalcineurinCalcineurin is a protein phosphatase also known as protein phosphatase 3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B . It activates the T cells of the immune system and can be blocked by drugs...
(protein phosphatase 2B) - GRK2Beta adrenergic receptor kinaseBeta adrenergic receptor kinase is a serine/threonine intracellular kinase. It is activated by PKA and its target is the beta adrenergic receptor...
(G-protein-coupled receptor kinase 2) - D2 dopamine receptorDopamine receptor D2Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
- IL1RAPL (interleukin-1 receptor accessory protein-like protein)
- PI4KIIIβ (type III phosphatidylinositol 4-kinase β)
- IP3 receptor (this activity is inhibited by lithium - a drug used for the treatment of bipolar disorderBipolar disorderBipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
) - 3',5'-cyclic nucleotide phosphodiesterasePhosphodiesteraseA phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
s - ARF1ARF1ADP-ribosylation factor 1 is a protein that in humans is encoded by the ARF1 gene.-Interactions:ARF1 has been shown to interact with GGA3, PLD2, COPB1 and Muscarinic acetylcholine receptor M3.-Further reading:...
(ADPAdenosine diphosphateAdenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
Ribosylation factor 1) - A type (Kv4.3KCND3Potassium voltage-gated channel subfamily D member 3 also known as Kv4.3 is a protein that in humans is encoded by the KCND3 gene. It contributes to the cardiac transient outward potassium current , the main contributing current to the repolarizing phase 1 of the cardiac action potential.- Function...
; Shal-related subfamily, member 3) voltage-gated potassium channelVoltage-gated potassium channelVoltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state....
s - Nitric oxide synthaseNitric oxide synthaseNitric oxide synthases are a family of enzymes that catalyze the production of nitric oxide from L-arginine. NO is an important cellular signaling molecule, having a vital role in many biological processes...
- TRPC5TRPC5Short transient receptor potential channel 5 also known as transient receptor protein 5 is a protein that in humans is encoded by the TRPC5 gene. TrpC5 is subtype of the TRPC family of mammalian transient receptor potential ion channels.- Function :TrpC5 is one of the seven mammalian TRPC proteins...
channel
- Calcineurin
- Frq modulates Ca2+ entry through a functional interaction with the α1 voltage-gated Ca2+-channel subunit.
History
NCS-1 was originally discovered in DrosophilaDrosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
as a mutation associated with calcium stimulated increases in neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
. Later work in bovine chromaffin cell
Chromaffin cell
Chromaffin cells are neuroendocrine cells found in the medulla of the adrenal gland and in other ganglia of the sympathetic nervous system. They are modified post-synaptic sympathetic neurons that receive sympathetic input...
s confirmed NCS-1 as a modulator of neurotransmission. The designation 'NCS-1' came from the assumption that the protein was expressed only in neuronal cell types, which is not the case.
Clinical significance
The expression of NCS-1 increases in bipolar disorderBipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
and some forms of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and decreases in inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
. NCS-1 has also been linked with Autism: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866544/?tool=pubmed.