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 In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

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. Expression was found in different neurons than that of the similar vitamin D-dependent calcium-binding protein,

calbindin Calbindins are three different calcium-binding proteins: calbindin 1, calbindin, calretinin and S100G. They were originally described as vitamin D-dependent calcium-binding proteins in the intestine and kidney of chicks and mammals. They are now ...

-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 neuron ...

. 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 is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of Antibody, antibodies binding specifically to antigens in biological tissues. Alber ...

, 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 ...

and in malignant mesothelioma and can be used to help differentiate different lung tumours. Antibodies to calretinin can also be used to distinguish between different types of brain tumour, demonstrating only those with

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

al rather than

glial Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cell (biology), cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce Action potential, electrical ...

, 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) an ...

and rarely seen ganglion cells. The presence of ganglion cells consistently correlated with calretinin-positive thin nerve fibrils in the

lamina propria The lamina propria is a thin layer of connective tissue that forms part of the moist linings known as mucous membranes or mucosae, which line various tubes in the body, such as the respiratory tract, the gastrointestinal tract, and the urogenital ...

muscularis mucosae The muscularis mucosae (or lamina muscularis mucosae) is a thin layer ( lamina) of muscle of the gastrointestinal tract, located outside the lamina propria, and separating it from the submucosa. It is present in a continuous fashion from the esop ...

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 (: rectums or recta) is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. Before expulsion through the anus or cloaca, the rectum stores the feces temporarily. The adult ...

. 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 ...

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