# PVALB

## Overview
The PVALB gene encodes the protein parvalbumin, a member of the EF-hand superfamily of calcium-binding proteins. Parvalbumin is characterized by its ability to bind calcium ions, playing a crucial role in modulating intracellular calcium levels across various tissues. This protein is particularly significant in muscle and neuronal tissues, where it facilitates muscle relaxation and influences synaptic plasticity, respectively. In the brain, parvalbumin is predominantly expressed in GABAergic neurons, contributing to the regulation of synaptic transmission and network properties. Alterations in PVALB expression have been associated with several neuropsychiatric disorders, including schizophrenia and autism spectrum disorder, highlighting its importance in maintaining normal neurological function (Belge2007Renal; Ruden2020Parvalbumin). Additionally, PVALB has been implicated in mitochondrial dynamics and cellular morphology, further underscoring its diverse physiological roles (Lichvarova2018Parvalbumin).

## Structure
The human PVALB gene encodes the protein parvalbumin, which is a member of the EF-hand superfamily of calcium-binding proteins. The primary structure of parvalbumin consists of a sequence of amino acids that form specific domains known for their calcium-binding capabilities. The protein contains three EF-hand domains, which are helix-loop-helix structures that facilitate calcium binding, although the AB site is nonfunctional (Babini2004Solution).

The secondary structure of human β-parvalbumin is characterized by eight α-helices, which are typical of EF-hand proteins (Babini2004Solution). The tertiary structure involves the folding of these helices, contributing to the protein's stability and function. The solution structure of human β-parvalbumin has been determined using NMR spectroscopy, revealing a backbone root-mean-square deviation (rmsd) of 0.50 Å, indicating a well-defined structure (Babini2004Solution).

Human β-parvalbumin does not exhibit significant quaternary structure, as it functions primarily as a monomer. The protein is subject to post-translational modifications, such as phosphorylation, which may influence its calcium-binding properties and interactions with other proteins (Lee2006Molecular). The structural data suggest a specialized physiological role, particularly in the mammalian auditory system (Babini2004Solution).

## Function
Parvalbumin (PVALB) is a calcium-binding protein that plays a crucial role in various cellular processes by modulating intracellular calcium (Ca2+) levels. It is part of the EF-hand Ca2+-binding protein superfamily, characterized by its ability to bind Ca2+ ions with high affinity, leading to conformational changes that influence cellular activities (Belge2007Renal). In muscle fibers, particularly fast-twitch muscles, PVALB facilitates the diffusion of Ca2+ from myofibrils to the sarcoplasmic reticulum, aiding in muscle relaxation (Belge2007Renal). In the brain, PVALB is expressed in GABAergic neurons, where it influences short-term synaptic plasticity and network properties, with its absence linked to increased susceptibility to epileptic seizures (Belge2007Renal).

PVALB also plays a significant role in mitochondrial dynamics and cell morphology. It affects mitochondrial volume and dynamics by decreasing fusion rates and increasing mitophagy, which is the selective elimination of damaged mitochondria (Lichvarova2018Parvalbumin). This regulation is crucial for maintaining mitochondrial health and homeostasis, impacting cell morphology and potentially influencing cytoskeleton dynamics (Lichvarova2018Parvalbumin). In renal epithelial cells, PVALB functions as a Ca2+ shuttle, modulating intracellular Ca2+ signaling in response to ATP, which affects the expression of the Na+-Cl- cotransporter in the distal convoluted tubule (Belge2007Renal).

## Clinical Significance
Alterations in the expression of the PVALB gene, which encodes the calcium-binding protein parvalbumin, have been implicated in several neuropsychiatric disorders. In schizophrenia, reduced levels of PVALB mRNA are observed in specific brain regions, potentially due to DNA hypermethylation, which is associated with a reduction in parvalbumin-expressing interneurons (PV-INs) and altered gamma oscillations (Fachim2018Parvalbumin; Ruden2020Parvalbumin). This hypermethylation of the PVALB promoter in the hippocampus is suggested to contribute to the reduced expression of parvalbumin, impacting GABAergic neurotransmission and potentially leading to cognitive disturbances and dopaminergic hyperfunction (Fachim2018Parvalbumin).

In Alzheimer's disease, changes in PV-INs are linked to disrupted gamma oscillations and abnormalities in the default mode network (Ruden2020Parvalbumin). Autism spectrum disorder also shares PV-IN abnormalities with schizophrenia, with several mouse models showing reduced PV-INs or decreased PV immunoreactivity (Ruden2020Parvalbumin). Additionally, PV knockout mice exhibit behaviors similar to those observed in autism spectrum disorder (Ruden2020Parvalbumin).

Beyond neuropsychiatric disorders, PVALB expression has been studied in the context of thyroid cancer. In follicular thyroid carcinoma cells, PVALB expression affects calcium dynamics and mitochondrial characteristics, potentially impacting cell proliferation and survival (Mendes2016PVALB). These findings suggest that PVALB may play a role in altering cellular processes relevant to cancer progression (Mendes2016PVALB).

## Interactions
Parvalbumin (PVALB) is a calcium-binding protein that plays a significant role in modulating calcium ion concentrations within cells, which is crucial for both muscle relaxation and neuronal signaling. In the context of neuronal function, PVALB interacts with calcium ions to influence presynaptic calcium signaling, particularly in molecular layer interneurons (MLIs) and Purkinje cells in the cerebellum. This interaction affects the kinetics of calcium transients, with PVALB contributing to the biexponential decay of calcium signals, which is essential for synaptic transmission and plasticity (Collin2005Developmental).

PVALB also interacts with other calcium-binding proteins such as calbindin (CB) in specific neuronal populations, although MLIs express only PVALB and not CB. This selective expression pattern influences the decay kinetics of calcium transients, with PVALB playing a critical role in shaping the calcium signaling dynamics in these cells (Collin2005Developmental).

In the reticular thalamic nucleus (RTN), PVALB modulates the firing properties of neurons by affecting the decay phase of intracellular calcium concentration, which in turn influences short-term plasticity and the firing patterns of RTN neurons (Albéri2013The).


## References


[1. (Lichvarova2018Parvalbumin) Lucia Lichvarova, Thomas Henzi, Dzhamilja Safiulina, Allen Kaasik, and Beat Schwaller. Parvalbumin alters mitochondrial dynamics and affects cell morphology. Cellular and Molecular Life Sciences, 75(24):4643–4666, September 2018. URL: http://dx.doi.org/10.1007/s00018-018-2921-x, doi:10.1007/s00018-018-2921-x. This article has 12 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1007/s00018-018-2921-x)

[2. (Babini2004Solution) Elena Babini, Ivano Bertini, Francesco Capozzi, Cristina Del Bianco, Dominik Hollender, Tamas Kiss, Claudio Luchinat, and Alessandro Quattrone. Solution structure of human β-parvalbumin and structural comparison with its paralog α-parvalbumin and with their rat orthologs,. Biochemistry, 43(51):16076–16085, December 2004. URL: http://dx.doi.org/10.1021/bi048388o, doi:10.1021/bi048388o. This article has 26 citations and is from a peer-reviewed journal.](https://doi.org/10.1021/bi048388o)

[3. (Mendes2016PVALB) Thais Biude Mendes, Bruno Heidi Nozima, Alexandre Budu, Rodrigo Barbosa de Souza, Marcia Helena Braga Catroxo, Rosana Delcelo, Marcos Leoni Gazarini, and Janete Maria Cerutti. Pvalb diminishes [ca2+] and alters mitochondrial features in follicular thyroid carcinoma cells through akt/gsk3β pathway. Endocrine-Related Cancer, 23(9):769–782, September 2016. URL: http://dx.doi.org/10.1530/erc-16-0181, doi:10.1530/erc-16-0181. This article has 9 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1530/erc-16-0181)

[4. (Lee2006Molecular) Shyh‐Jye Lee, Chi‐Ching Ju, Shian‐Ling Chu, Ming‐Shan Chien, Tun‐Hao Chan, and Wen‐Liang Liao. Molecular cloning, expression and phylogenetic analyses of parvalbumin in tilapia, oreochromis mossambicus. Journal of Experimental Zoology Part A: Ecological Genetics and Physiology, 307A(1):51–61, December 2006. URL: http://dx.doi.org/10.1002/jez.a.345, doi:10.1002/jez.a.345. This article has 9 citations and is from a peer-reviewed journal.](https://doi.org/10.1002/jez.a.345)

[5. (Ruden2020Parvalbumin) Jacob B. Ruden, Laura L. Dugan, and Christine Konradi. Parvalbumin interneuron vulnerability and brain disorders. Neuropsychopharmacology, 46(2):279–287, July 2020. URL: http://dx.doi.org/10.1038/s41386-020-0778-9, doi:10.1038/s41386-020-0778-9. This article has 119 citations and is from a highest quality peer-reviewed journal.](https://doi.org/10.1038/s41386-020-0778-9)

[6. (Fachim2018Parvalbumin) Helene A Fachim, Umarat Srisawat, Caroline F Dalton, and Gavin P Reynolds. Parvalbumin promoter hypermethylation in postmortem brain in schizophrenia. Epigenomics, 10(5):519–524, April 2018. URL: http://dx.doi.org/10.2217/epi-2017-0159, doi:10.2217/epi-2017-0159. This article has 31 citations and is from a peer-reviewed journal.](https://doi.org/10.2217/epi-2017-0159)

[7. (Belge2007Renal) Hendrica Belge, Philippe Gailly, Beat Schwaller, Johannes Loffing, Huguette Debaix, Eva Riveira-Munoz, Renaud Beauwens, Jean-Pierre Devogelaer, Joost G. Hoenderop, René J. Bindels, and Olivier Devuyst. Renal expression of parvalbumin is critical for nacl handling and response to diuretics. Proceedings of the National Academy of Sciences, 104(37):14849–14854, September 2007. URL: http://dx.doi.org/10.1073/pnas.0702810104, doi:10.1073/pnas.0702810104. This article has 81 citations.](https://doi.org/10.1073/pnas.0702810104)

[8. (Albéri2013The) Lavinia Albéri, Alessandra Lintas, Robert Kretz, Beat Schwaller, and Alessandro E. P. Villa. The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons. Journal of Neurophysiology, 109(11):2827–2841, June 2013. URL: http://dx.doi.org/10.1152/jn.00375.2012, doi:10.1152/jn.00375.2012. This article has 38 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1152/jn.00375.2012)

[9. (Collin2005Developmental) Thibault Collin, Mireille Chat, Marie Gabrielle Lucas, Herman Moreno, Peter Racay, Beat Schwaller, Alain Marty, and Isabel Llano. Developmental changes in parvalbumin regulate presynaptic ca2+signaling. The Journal of Neuroscience, 25(1):96–107, January 2005. URL: http://dx.doi.org/10.1523/jneurosci.3748-04.2005, doi:10.1523/jneurosci.3748-04.2005. This article has 152 citations.](https://doi.org/10.1523/jneurosci.3748-04.2005)