Parvalbumin (PV) is a calcium-binding protein with low molecular weight (typically 9–11 kDa). In humans, it is encoded by the PVALB gene. It is a member of the albumin family; it is named for its size (parv-, from Latin parvus which means "small") and its ability to coagulate. It has three EF hand motifs and is structurally related to calmodulin and troponin C. Parvalbumin is found in fast-contracting muscles, where its levels are highest, as well as in the brain and some endocrine tissues.
Structure Parvalbumin is a small, stable protein containing EF-hand type calcium binding sites. It is involved in calcium signaling. 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.
Tissue distribution
In neural tissue Parvalbumin is present in some GABAergic interneurons in the nervous system, especially the reticular thalamus, and expressed predominantly by chandelier and basket cells in the cortex. In the cerebellum, PV is expressed in Purkinje cells and molecular layer interneurons. In the hippocampus, PV+ interneurons are subdivided into basket, axo-axonic, and bistratified cells, each subtype targeting distinct compartments of pyramidal cells. 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 waves recorded in EEG. PV-expressing interneurons represent approximately 25% of GABAergic cells in the primate DLPFC. Other calcium-binding protein markers are calretinin (most abundant subtype in DLPFC, about 50%) and calbindin. Interneurons are also divided into subgroups by the expression of neuropeptides such as somatostatin, neuropeptide Y, cholecystokinin.
In muscular tissue PV is known to be involved in relaxation of fast-twitch muscle fibers. This function is associated with the PV role in calcium sequestration.
Function Calcium binding proteins like parvalbumin play a role in many physiological processes, namely cell-cycle regulation, second messenger production, muscle contraction, organization of microtubules and phototransduction. 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. During muscle contraction, the action potential stimulates voltage-sensitive proteins in the T-tubule membrane. These proteins stimulate the opening of Ca2+ channels in the sarcoplasmic reticulum, leading to release of Ca2+ in the sarcoplasm. The Ca2+ ions bind to troponin, which causes the displacement of tropomyosin, a protein that prevents myosin walking along actin. 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.
Clinical significance Decreased PV and GAD67 expression was found in PV+ GABAergic interneurons in schizophrenia. Parvalbumin has been identified as the major allergen causing fish meat allergy (but not shellfish allergy). Most bony fishes manifest β-parvalbumins as major allergens and cartilaginous fishes such as sharks and rays manifest α-parvalbumins as major allergens; allergenicity to bony fishes has a low cross-reactivity to cartilaginous fishes and also chicken meat.
Evolution
Parvalbumins and their genes have only been found in jawed vertebrate species so far. From the evolutionary level of sharks, already three major lineages of parvalbumins can be distinguished: (1) α-parvalbumins, which include the above discussed human "parvalbumin"; (2) oncomodulins (sometimes called "β-1 parvalbumins"), which are also found in human and mouse; and (3) β-2 parvalbumins, which are the major allergens in most bony fish and were lost in human and mouse but conserved in some primitive mammals. All parvalbumins share a highly conserved structure (see the figure), which explains their high level of sequence conservation, resulting in the above-mentioned cross-reactivity in allergenic reactions against different bony fish species and even species from other animal clades such as chicken. Bony fishes have, depending on the species, combined for all three parvalbumin lineages between 7 and 22 genes. Although in most bony fishes the β-2 parvalbumins are the major allergens, in some bony fishes the α-parvalbumins are the highest expressed in muscle and were identified as the allergens. The allergen nomenclature is partly based on the order of allergen detection per species, and therefore identical allergen numbers in different fish species do not always refer to the same gene (see the table).
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.
See also Parve101q, an experimental modification of Parvalbumin.
References
External links Parvalbumins at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Baig I, Bertini I, Del Bianco C, Gupta YK, Lee YM, Luchinat C, et al. (May 2004). "Paramagnetism-based refinement strategy for the solution structure of human alpha-parvalbumin". Biochemistry. 43 (18): 5562–5573. doi:10.1021/bi035879k. PMID 15122922.
