Parvalbumin (PV) is a

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

-binding protein with low molecular weight (typically 9-11 kDa). In humans, it is encoded by the ''PVALB'' gene. It is not a member of the

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

family; it is named for its size (''parv-'', from Latin ''parvus'' small) and its ability to coagulate. It has three

EF hand The EF hand is a helix–loop–helix structural domain or ''motif'' 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 ...

motifs and is structurally related to

calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the bind ...

and

troponin C Troponin C is a protein which is part of the troponin complex. It contains four calcium-binding EF hands, although different isoforms may have fewer than four functional calcium-binding subdomains. It is a component of thin filaments, along wit ...

. Parvalbumin is found in fast-contracting muscles, where its levels are highest, as well as in the brain and some endocrine tissues. Parvalbumin is a small, stable protein containing EF-hand type calcium binding sites. It is involved in

calcium signaling Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allos ...

. Typically, this protein is broken into three domains, domains AB, CD and EF, each individually containing a helix-loop-helix motif. The AB domain houses a two amino-acid deletion in the loop region, whereas domains CD and EF contain the N-terminal and C-terminal, respectively. Calcium binding proteins like parvalbumin play a role in many physiological processes, namely cell-cycle regulation,

second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...

production,

muscle contraction Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as ...

, organization of

microtubules Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...

and

phototransduction Visual phototransduction is the transduction (physiology), sensory transduction process of the visual system by which light is detected to yield Action potential, nerve impulses in the rod cells and cone cells in the retina of the eye in humans and ...

. Therefore, calcium-binding proteins must distinguish calcium in the presence of high concentrations of other metal ions. The mechanism for the calcium selectivity has been extensively studied.

Location and function

Parvalbumin in neural tissue

Parvalbumin is present in some GABAergic

interneuron Interneurons (also called internuncial neurons, relay neurons, association neurons, connector neurons, intermediate neurons or local circuit neurons) are neurons that connect two brain regions, i.e. not direct motor neurons or sensory neurons. I ...

s in the nervous system, especially the reticular thalamus, and expressed predominantly by

chandelier A chandelier (; also known as girandole, candelabra lamp, or least commonly suspended lights) is a branched ornamental light fixture designed to be mounted on ceilings or walls. Chandeliers are often ornate, and normally use incandescent li ...

and

basket cell Basket cells are inhibitory GABAergic interneurons of the brain, found throughout different regions of the cortex and cerebellum. Anatomy and physiology Basket cells are multipolar GABAergic interneurons that function to make inhibitory synapses ...

s in the cortex. In the

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...

, PV is expressed in

Purkinje cell Purkinje cells, or Purkinje neurons, are a class of GABAergic inhibitory neurons located in the cerebellum. They are named after their discoverer, Czech people, Czech anatomist Jan Evangelista Purkyně, who characterized the cells in 1839. Stru ...

s and molecular layer interneurons. In the

hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...

, PV+ interneurons are subdivided into basket, axo-axonic, and bistratified cells, each subtype targeting distinct compartments of pyramidal cells.free full text
/ref> PV interneurons' connections are mostly perisomatic (around the cell body of neurons). Most of the PV interneurons are fast- spiking. They are also thought to give rise to

gamma wave A gamma wave or gamma Rhythm is a pattern of neural oscillation in humans with a frequency between 25 and 140 Hz, the 40- Hz point being of particular interest. Gamma rhythms are correlated with large scale brain network activity and cognitive ...

s recorded in

EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...

. PV-expressing interneurons represent approximately 25% of GABAergic cells in the

primate Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including huma ...

DLPFC. Other calcium-binding protein markers are

calretinin Calretinin, also known as calbindin 2 (formerly 29 kDa calbindin), is a calcium-binding protein involved in calcium signaling. In humans, the calretinin protein is encoded by the ''CALB2'' gene. Function This gene encodes an intracellular ca ...

(most abundant subtype in DLPFC, about 50%) and

calbindin Calbindins are three different calcium-binding proteins: calbindin, calretinin and S100G. They were originally described as vitamin D-dependent calcium-binding proteins in the intestine and kidney in the chick and mammals. They are now classi ...

. Interneurons are also divided into subgroups by the expression of neuropeptides such as

somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...

neuropeptide Y Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. NPY has been identified as the most abundant peptide present in the ma ...

cholecystokinin Cholecystokinin (CCK or CCK-PZ; from Greek ''chole'', "bile"; ''cysto'', "sac"; ''kinin'', "move"; hence, ''move the bile-sac (gallbladder)'') is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and ...

Parvalbumin in muscular tissue

PV is known to be involved in relaxation of

fast-twitch muscle A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small Cell (biology), cells. A skeletal muscle, skeletal muscle cell is long and threadlike with mu ...

fibers. This function is associated with PV role in calcium sequestration. During

, the

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

stimulate voltage-sensitive proteins in

T-tubules T-tubules (transverse tubules) are extensions of the cell membrane that penetrate into the center of skeletal and cardiac muscle cells. With membranes that contain large concentrations of ion channels, transporters, and pumps, T-tubules permit ...

membrane. These proteins stimulate the opening of Ca²⁺ channels in the

sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other Cell (biology), cells. The main function of the SR is to store calcium ions (Ca2+). Calcium in bio ...

, leading to release of Ca²⁺ in the sarcoplasm. The Ca²⁺ ions bind to

troponin image:Troponin Ribbon Diagram.png, 400px, Ribbon representation of the human cardiac troponin core complex (52 kDa core) in the calcium-saturated form. Blue = troponin C; green = troponin I; magenta = troponin T.; ; rendered with PyMOL Troponin, ...

, what causes the displacement of

tropomyosin Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in actin-based cytoskeletons. Tropomyosin and the actin skeleton All organisms contain organelles that provide physical integrity to their cells. These type of organelles ar ...

, a protein that prevents

myosin Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility. The first myosin ...

walking along

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

. The displacement of tropomyosin exposes the myosin-binding sites on actin, permitting muscle contraction. This way, while muscle contraction is driven by Ca²⁺ release, muscle relaxation is driven by Ca²⁺ removal from sarcoplasm. Along with Ca²⁺ pumps, PV contributes to Ca²⁺ removal from cytoplasm: PV binds to Ca²⁺ ions in the sarcoplasm, and then shuttles it to the sarcoplasmic reticulum.

Role in pathology

Decreased PV and

GAD67 Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme that catalyzes the decarboxylation of glutamate to gamma-aminobutyric acid (GABA) and carbon dioxide (). GAD uses pyridoxal-phosphate (PLP) as a cofactor. The reaction p ...

expression was found in PV+ GABAergic interneurons in

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

Parvalbumin and food allergy

Parvalbumin has been identified as an

allergen An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies. In technical terms ...

causing

fish allergy A food allergy is an abnormal immune response to food. The symptoms of the allergic reaction may range from mild to severe. They may include itchiness, swelling of the tongue, vomiting, diarrhea, hives, trouble breathing, or low blood pressur ...

(but not shellfish allergy). Bony fishes manifest β-parvalbumin and cartilaginous fishes such as sharks and rays manifest α-parvalbumin; allergenicity to bony fishes has a low cross-reactivity to cartilaginous fishes.

History

The protein was discovered in 1965 as a component of the fast-twitching white muscle of fish. It was described as a low molecular-weight "albumin". It is unknown who coined the term ''parvalbumin'', but the word is already in use by 1967.

References

External links

* * {{Albumins Molecular neuroscience EF-hand-containing proteins Articles containing video clips