Calretinin, also known as calbindin 2 (formerly 29 kDa calbindin), is a

calcium-binding protein Calcium-binding proteins are proteins that participate in calcium cell signalling pathways by binding to Ca2+, the calcium ion that plays an important role in many cellular processes. Calcium-binding proteins have specific domains that bind to cal ...

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 all ...

. In humans, the calretinin protein is encoded by the ''CALB2''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Function

This gene encodes an intracellular calcium-binding protein belonging to the troponin C superfamily. Members of this protein family have six

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 ...

domains which bind calcium. This protein plays a role in diverse cellular functions, including message targeting and intracellular calcium buffering. Calretinin is abundantly expressed in neurons including retina (which gave it the name) and cortical

interneurons 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 ...

. Expression was found in different neurons than that of the similar vitamin D-dependent calcium-binding protein, calbindin-28kDa. Calretinin has an important role as a modulator of neuronal excitability including the induction of

long-term potentiation In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...

. Loss of expression of calretinin in hippocampal interneurons has been suggested to be relevant in temporal lobe epilepsy. It is expressed in a number of other locations including hair follicles.

Clinical significance

Calretinin is a diagnostic marker for some human diseases, including Hirschsprung disease and some cancers.

Mesothelioma

Using

immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to a ...

, calretinin can be demonstrated in both benign

mesothelium The mesothelium is a membrane composed of simple squamous epithelium, simple squamous epithelial cells of mesodermal origin, which forms the lining of several body cavities: the pleura (pleural cavity around the lungs), peritoneum (abdominopelvic c ...

and in malignant

mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall. Less commonly the lining ...

and can be used to help differentiate different

lung tumour Lung tumors are neoplastic lung nodules. These include: Primary tumors of the lung/pulmonary system: * Bronchial leiomyoma, a rare, benign tumor * Lung cancer, the term commonly used to refer to ''carcinoma of the lung'' * Pulmonary carcinoid tu ...

s. Antibodies to calretinin can also be used to distinguish between different types of brain tumour, demonstrating only those with

neuron A neuron, neurone, or nerve cell is an membrane potential#Cell excitability, electrically excitable cell (biology), cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous ...

al rather than

glial Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form m ...

, differentiation. Furthermore, the essential function of calretinin in mesothelioma cell lines has been demonstrated ''in vitro'' and may be an interesting target for therapeutical approaches.

Hirschsprung disease

In Hirschsprung disease, calretinin

offers additional diagnostic value in specimens with inadequate amount of

submucosa The submucosa (or tela submucosa) is a thin layer of tissue in various organs of the gastrointestinal, respiratory, and genitourinary tracts. It is the layer of dense irregular connective tissue that supports the mucosa (mucous membrane) and ...

and rarely seen

ganglion A ganglion is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system there are both sympath ...

cells. The presence of ganglion cells consistently correlated with calretinin-positive thin nerve fibrils in the lamina propria, muscularis mucosae and superficial submucosa. These calretinin-positive thin neurofibrils are absent in the aganglionic segments of bowel and in the areas without ganglion cells from the junction of normal with diseased

rectum The rectum is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the sigmoid colon) at the l ...

. Calretinin is strongly expressed in the submucosal and

subserosa The subserosa or tela subserosa, is a thin layer of tissue in the walls of various organs. It is a layer of connective tissue (usually of the areolar type) between the muscular layer (muscularis externa) and the serosa (serous membrane). The su ...

l nerve trunks in the ganglionic segment. No calretinin expression is seen in the nerve trunks in the rest of the aganglionic segment. It has faint expression in the thick nerve trunks from the areas without ganglion cells. Faint positivity of the thick submucosal and subserosal nerves in the absence of ganglion cells and calretinin positive nerve fibrils, is characteristic of the junction of the aganglionic-to-normal rectum.

References

External links