Calretinin: from a "simple" Ca(2+) buffer to a multifunctional protein implicated in many biological processes

Our plain-English summary of Calretinin: from a "simple" Ca(2+) buffer to a multifunctional protein implicated in many biological processes, by B. Schwaller (Frontiers in Neuroanatomy, 2014).

The study

• Author: B. Schwaller
• Journal: Frontiers in Neuroanatomy
• Published: 2014;8:3
• Type of article: Review
• Cited by: 115 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The hexa-EF-hand Ca(2+)-binding protein calretinin (CR) is predominantly expressed in specific neurons of the central and peripheral nervous system. However, CR expression is also observed in non-neuronal cells, e.g., during embryonic development and in mesothelioma cells. Of the 6 EF-hand domains, 5 are functional; the first 4 domains form 2 pairs showing high cooperativity within a pair that results in non-linear modulation of intracellular Ca(2+) signals by CR. EF-hand domain 5 has a low affinity and represents the identified interaction site with CR-binding partners present in mouse cerebellar granule cells. CR binding to other targets including the pore-forming α1 subunit of the Ca(2+) channel Ca V 2.1, as well as to huntingtin indicates additional Ca(2+) sensor functions besides the well-known Ca(2+)-buffering functions. The absence of CR in cerebellar granule cells of CR(-/-) mice results in increased excitability and altered firing of Purkinje cells and promotes cerebellar 160-Hz oscillations impairing motor coordination. The putative role of CR in neuroprotection is still highly discussed. Altogether, CR emerges as a multi-functional protein also associated with development, i.e., cell proliferation, differentiation, and cell death.

In plain English

This article was a short review (a "mini review"), not a new study. It summarized published research on calretinin, a calcium-binding protein found mainly in certain nerve cells but also in mesothelioma cells. The review described the protein's calcium-binding sites and cited earlier studies identifying two proteins it binds: part of a calcium channel and huntingtin. Citing mouse studies, it reported that the absence of calretinin in cerebellar granule cells was linked to increased excitability and impaired motor coordination. On asbestos, the review cited a 2009 laboratory study in which higher calretinin levels strongly correlated with increased resistance to asbestos cytotoxicity in immortalized Met-5A mesothelial cells. That protective effect was lost when PI3K inhibitors were present. The asbestos fiber type was not named. The review also cited work in which lowering calretinin caused a G1 block in mesothelial cells and led to apoptosis in mesothelioma-derived cells. The author suggested that calretinin down-regulation might be viewed as a potential new target for malignant mesothelioma therapy. The author concluded that the protein's likely many functions are only starting to be unravelled.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Mini review of published research on the protein calretinin (no new data reported)
• Who was studied: No study population; the review summarized earlier laboratory, cell-culture and mouse studies on calretinin
• Exposure: Not an exposure study. Asbestos appears only in a cited laboratory study of asbestos cytotoxicity in immortalized Met-5A mesothelial cells; no fiber type or dose is given in this article
• Main results:
  • The review cited a study (Henzi et al., 2009) reporting that increased calretinin expression strongly correlated with increased resistance to asbestos cytotoxicity in immortalized Met-5A mesothelial cells
  • According to the cited work, this protective effect in mesothelial cells was abolished in the presence of PI3K inhibitors
  • The review cited work (Blum and Schwaller, 2013) in which calretinin down-regulation caused a G1 block in calretinin-expressing mesothelial cells and led to apoptosis in mesothelioma-derived cells
  • Identified calretinin binding partners listed in the review were the alpha-1 subunit of the CaV2.1 calcium channel and huntingtin
  • Cited studies in mice lacking calretinin linked increased excitability of cerebellar granule cells to altered Purkinje cell firing and impaired motor coordination
  • On a possible role of calretinin in protecting nerve cells, the review stated that reports for and against such a role were split almost 50:50
• The authors' conclusion: The author suggested that, in calretinin-expressing mesothelial and mesothelioma cells, calretinin down-regulation might be viewed as a potential new target or strategy for malignant mesothelioma therapy. The author concluded that the likely many functions of calretinin are only beginning to be unravelled.
• Limitations the authors state:
  • The author stated that detailed analyses of calretinin expression in the brain were not covered in this mini review
  • The author noted that no structural data on full-length calretinin had been reported

Topics

Medical terms in this study, explained in our Lexicon: Calretinin, Mesothelioma.

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