UNIPROT:P10721 - FACTA Search

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Query: UNIPROT:P10721 (c-kit)
6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The substance P (SP)-containing nerves at the deep (DMP) and myenteric (MP) plexuses and the related interstitial cells of Cajal (ICC-DMP and ICC-MP) were immunohistochemically studied in rat and guinea-pig ileum. All the ICC expressed SP-preferred receptor NK1r: the ICC-DMP showed an intense and the ICC-MP a faint NK1r-immunoreactivity(IR). c-kit-labeling confirmed that they were ICC. The SP-IR nerves at the DMP were significantly more numerous in the guinea-pig than in the rat, and more numerous than those at the MP in both animal species. All the ICC-DMP in the guinea-pig and half of them in the rat were close to SP-IR nerves. The ICC-MP were rarely near to SP-IR nerves in either species. The SP-innervation shows interspecies differences at the DMP that imply a different tachykinergic control of the local ICC.
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PMID:Substance P immunoreactive nerves and interstitial cells of Cajal in the rat and guinea-pig ileum. A histochemical and quantitative study. 1040 75

The relationship between the development of the enteric nervous system and interstitial cells of Cajal (ICC) in the human small intestine was investigated in a full-term infant who presented with intestinal pseudo-obstruction. Immunohistochemistry revealed absence of enteric nerves and ganglia but abundant c-Kit immunoreactivity associated with Auerbach's plexus (ICC-AP). However, c-Kit immunoreactivity associated with the deep muscular plexus (ICC-DMP) and intermuscular ICC was absent. Electron microscopy showed ICC-AP with a normal ultrastructure; ICC-DMP were seen but were severely injured, suggesting degeneration. In vitro recording of intestinal muscle showed slow wave activity as well as response to cholinergic stimulation. Fluoroscopic examination of the small bowel showed a variety of motor patterns, including rhythmic, propagating contractions. In conclusion, total absence of enteric nerves was associated with absence of normal ICC-DMP. However, a normal musculature, including a network of ICC-AP, allowed for generation of rhythmic, propagating contractile activity, suggesting the presence of functional motor activity.
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PMID:Development of interstitial cells of Cajal in a full-term infant without an enteric nervous system. 1115 97

With functional evidence emerging that interstitial cells of Cajal (ICC) play a role in smooth muscle innervation, detailed knowledge is needed about the structural aspects of enteric innervation of the human gut. Conventional electronmicroscopy (EM), immunohistochemistry and immuno-EM were performed on the musculature of the distal human ileum focusing on ICC associated with the deep muscular plexus (ICC-DMP) and intramuscular ICC (ICC-IM). ICC-DMP could be identified by EM but not by c-Kit immunohistochemistry. Immuno-EM revealed that ICC-DMP were innervated by both cholinergic and nitrergic nerves, and were the only cells to possess specialized synapse-like junctions with nerve varicosities and gap junction contacts with smooth muscle cells. c-Kit positive ICC near the deep muscular plexus were not ICC-DMP, but ICC-IM located in septa. ICC-IM were innervated by both cholinergic and nitrergic nerves but without specialized contacts. Varicosities of both nerve types were also found scattered throughout the musculature without specialized contact with any ICC. No ICC showed immunoreactivity for neuronal nitric oxide synthase. As ICC-DMP form synapse-like junctions with cholinergic and nitrergic nerves and gap junction contacts with muscle cells, it is hypothesized that ICC-DMP hold a specialized function related to innervation of smooth muscle of the human intestine.
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PMID:Cholinergic and nitrergic innervation of ICC-DMP and ICC-IM in the human small intestine. 1450 53

Interstitial cells of Cajal (ICC) are involved in the generation of electrical rhythmicity of intestinal muscle and in the transduction of neural inputs in the gut. Although the expression of receptors for neurotransmitters and hormones and some second messengers have been investigated in ICC, the protein kinases present in these cells have not been well documented. This study has demonstrated the immunohistochemical localisation of PKA, PKC gamma and PKC theta in ICC that were identified by the known ICC marker, c-Kit, in the guinea-pig gut. Other PKCs, PKC alpha, beta, delta, epsilon, eta, iota and lambda, and Ca(2+)-calmodulin-dependent protein kinase II were not localised in ICC. Double labelling studies were conducted on longitudinal muscle-myenteric plexus and external muscle-myenteric plexus preparations of the oesophagus, stomach (fundus, corpus and antrum), duodenum, distal ileum, caecum, proximal and distal colon, and rectum. The three protein kinases were detected in c-Kit-immunoreactive ICC at the level of the myenteric plexus (IC-MY), in the muscle (IC-IM) and at the level of the deep muscular plexus (IC-DMP) in the small intestine. PKA was found in over 90% of IC-IM in all regions examined, and in over 90% of IC-MY in the gastric body and antrum and throughout the small and large intestines. PKC gamma was in the majority of ICC in the gastric body and antrum and in the small intestine, but was largely absent from ICC in the oesophagus, proximal stomach and large intestine. PKC theta occurred in the majority of ICC in all regions except the rectum. The intensity of staining was greatest for PKA, with PKC gamma giving comparatively weak labelling of ICC. PKA was also detected in myenteric neurons, smooth muscle, macrophages and fibroblast-like cells. PKC gamma labelling occurred in large, multipolar neurons throughout the small and large intestine, as well as in lymph vessels and in capillaries. It is concluded that PKA, PKC gamma and PKC theta are all present in ICC, with the differences in their localisations suggesting specific roles for each in ICC function.
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PMID:Protein kinases expressed by interstitial cells of Cajal. 1465 70

In the wall of the digestive tract, there are pacemaker and conduction systems which can be compared with those in the heart. The introduction of c-Kit as a specific marker of the cells, ICCs, have dramatically clarified morphological and functional understanding of the cells. Mutant animals that lack c-Kit lose or decrease intestinal motility. Four classes of ICCs have been identified and these are distributed along the digestive tract in an organ- and tissue-specific manner: 1) IC-MY locate along the myenteric plexus; 2) IC-DMP, along the deep muscular plexus of small intestine; 3) IC-SMP, along the interface between the submucosa and circular muscle layer of large intestine; and 4) IC-IM, within the muscular layer of the stomach and large intestine. Basically, IC-MY and IC-SMP have pacemaker functions, whereas IC-DMP and IC-IM link signals between the enteric nervous system and smooth muscle cells (SMC). All classes of the cells are connected by gap junctions. Immunocytochemical observations using specific antibodies against various gap junction proteins, connexins (Cx), revealed that Cx43 was localized in the gap junctions between SMC and ICCs, whereas Cx45 was specifically expressed in IC-DMP as it is in the cardiac conduction systems. Mutant animals that we produced enabled us to show cells expressing Cx45 mRNA by replacing the Cx45 locus with a LacZ reporter gene and revealed that most of SMC express Cx45, where so far gap junctions were not demonstrated by electron microscopy or immunocytochemistry, probably due to their small size.
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PMID:[Networks of pacemaker cells for gastrointestinal motility]. 1499 24

The tachykinin substance P (SP) acts on the gut muscle coat via its preferred receptor, neurokinin 1 (NK1r). In the mouse ileum, NK1r-immunoreactivity (NK1r-IR) was detected in neurons, in the interstitial cells of Cajal at the deep muscular plexus (ICC-DMP) and the myoid cells of the villi. SP-IR was detected in neurons and varicose nerve fibers, which were especially numerous at the DMP and closely associated with the ICC-DMP. In mice with a mutation in the W locus (ckit mutant animals), innervation is suggested to be normal although few studies have actually tested this hypothesis. Indeed, studies demonstrating ICC-DMP integrity are lacking and whether SP- and NK1r-IR are normal in these animals has not been investigated. Our aim was to perform an immunohistochemical study on the ileum of a strain of heterozygous mice with a mutation in the W locus, the W(e/+) mice, to test this hypothesis. SP-IR nerve fibers were significantly more numerous than in wild type mice; NK1r-IR was clustered on the plasma membrane and also intracytoplasmatic in the neurons, but absent in the ICC-DMP. The richness in SP-IR nerve fibers and the NK1r-IR distribution in the neurons, similar to that of activated cells, might be attempts to compensate for the SP preferred receptor absence at the ICC-DMP. In conclusion, SP content and NK1r expression are noticeably different in c-kit mutants with respect to wild type mice, and probably causing an anomalous tachykininergic control of intestinal motility. Physiological studies on Wmutant mice have to take into account that innervation in this animal model is affected by the c-kit mutation.
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PMID:Substance P and Neurokinin 1 receptor - expression is affected in the ileum of mice with mutation in the W locus. 1679 16

The so-called interstitial cells of Cajal myenteric plexus (ICC-MP), interstitial cells of Cajal intramuscular (ICC-IM) and interstitial cells of Cajal deep muscular plexus (ICC-DMP) are the three types of ICC endowed within the intestinal muscle coat where they play different roles in gut motility. Studies on ICC ontogenesis showed ICC-MP in the human ileum by 7-9 weeks while information on ICC-IM and ICC-DMP in foetuses and newborns are not exhaustive. Functional recordings in the fasting state of prematurely born babies aged 28-37 weeks showed immature ileal motility. To gain more information on the time of appearance of the three ICC types in the human ileum and on the steps of the acquisition of mature features, we studied by c-kit immuno-histochemistry foetuses aged 17-27 weeks and newborns aged 36-41 weeks. In parallel, the maturative steps of enteric plexuses and muscle layers were immunohistochemically examined by using anti-neuron specific enolase (NSE), anti-S-100 and anti-alpha smooth muscle actin (alphaSMA) antibodies. The appearance and differentiation of all the ICC types were seen to occur in concomitance with those of the related nerve plexuses and muscle layers. ICC-MP appeared first, ICC-IM and ICC-DMP later and their differentiation was incomplete at birth. In conclusion, the ICC-MP, the intestinal pacemaker cells, in spite of absence of food intake, are already present during the foetal life and the ICC-IM appear by pre-term life, thus ensuring neurotransmission. The ICC-DMP and their related nerve plexus and smooth muscle cells, i.e. the intestinal stretch receptor, begin to differentiate at birth. These findings might help in predicting neonatal ileal motor behaviour and in interpreting the role of ICC abnormalities in the pathophysiology of intestinal motile disorders of neonates and young children.
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PMID:Morphology of the interstitial cells of Cajal of the human ileum from foetal to neonatal life. 1763 40

Interstitial cells of Cajal (ICC) are important regulatory cells generating electrical rhythmicity and transducing neural signals in the gastrointestinal musculature. ICC express the proto-oncogene c-kit, a receptor tyrosine kinase, and can be examined morphologically using the c-Kit antibody. The c-kit gene is allelic with the murine white-spotting locus W, and the c-kit mutation (W mutation) affects various aspects of hematopoietic cells, germ cells, melanocytes, mast cells, and ICC. Heterozygous W/W( v) mutant mice lack a specific type of ICC and have been used to reveal its function. To search for a new model that lacks a specific type of ICC, we examined homozygous W( v)/W( v) black-eyed-white mice that are viable with anemia. Results showed the principal patterns of ICC deficiency were the same between the W/W( v) and W( v)/W( v) mutants. In the stomach of both mice, intramuscular ICC (ICC-IM) were missing and myenteric ICC (ICC-MY) were reduced in number. In the small intestine, the number of ICC-MY was severely reduced in spite of a normal distribution of deep muscular plexus ICC (ICC-DMP). The cecum also exhibited fewer reduced. ICC-IM in the colon were almost entirely missing, whereas ICC-MY were reduced only in the distal colon. In the small intestine and colon, the number of remaining ICC-MY in W( v)/W( v) mice was greater than that in W/W( v) mice. The enteric nervous system of the two mutant mice showed normal characteristics. From these findings, we conclude that W( v)/W( v) mice represent a new genotype that lacks a part of the ICC in its gastrointestinal musculature.
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PMID:Interstitial cells of Cajal in the gastrointestinal musculature of W mutant mice. 1807 85

Gastrointestinal stromal tumor (GIST) is the most frequent spindle cell tumor in the gastrointestinal tract and may arise from esophagus to rectum. The stomach is the most frequent site, followed by small intestine, rectum, and esophagus. There have been some regional differences reported in their histopathologic and clinical presentations. The purpose of this study is to compare ultrastructural features of GIST, according to its anatomic site, in order to provide additional data to support the current concept of its histogenesis. Fifty-four GISTs (27 from stomach, 23 from small intestine, and 4 from rectum) were included in the study. Histopathologically, gastric GISTs tended to be more frequently epithelioid, particularly those in children, while small intestinal GISTs (SISTs) were mostly spindly in all but three cases. All four of the rectal GISTs were spindly. Ultrastructurally, there seem to be considerable regional differences. In the majority of gastric GISTs, in both epithelioid and spindle types, tumor cells exhibited focal features of myoid differentiation evidenced by the presence of incomplete external lamina (EL) and/or focal accumulations of thin fibers with interrupted electron densities consistent with actin filaments. However, features of myoid differentiation were exceptional for SISTs and rectal GISTs, being present in only one example in each. Some gastric GISTs, particularly those having an epithelioid appearance, showed cell borders luxuriously decorated by long filopods (anemone cell features). Anemone cell features were also present in spindle cell types of gastric GISTs as well as SISTs, albeit it was simpler and less luxuriant. Skeinoid fibers were present in the majority of SISTs and rectal GISTs, but absent in all gastric GISTs except one. These differences appeared to be too significant to propose a uniform histogenesis for all GISTs. Nevertheless, on closer analysis, certain features could be identified to explain a line of differentiation in all GISTs ranging from (1) polygonal uncommitted epithelioid mesenchymal cells with cell borders decorated by luxuriant fimbria, to (2) spindly tumor cells with less prominent fimbria, or (3) cells with or without features of minimum myoid differentiation characterized by the focal presence of cytoplasmic actin fibers or incomplete EL or skeinoid fibers, which might represent an altered product of EL protein. These findings led the author to speculate that the probable primordial cells of GIST may be the primitive mesenchymal cells, which have the potential to differentiate into myoid cells. In this regard, it is important to note that the putative primordial cell of GIST, interstitial cells of Cajal (ICC), and intestinal smooth muscle cells have been shown to develop from the common progenitor cells of the primitive gut, and c-Kit plays a crucial role in the determination of their fate to differentiate to muscle cells or ICC. The author concludes that all GISTs derive from stem cells in the gut retaining some of the differentiation potential seen in primitive gut cells. One of the likely candidates for such cells in the intestinal musculature is ICC-DMP (interstitial cells of Cajal associated with deep muscular plexus) identified as ICC having smooth muscle features identified exclusively by electron microscopy. These cells have been shown to have some of the features of muscle cells by the presence of external lamina and less well-organized cytoplasmic filaments; they also express CD117 in the cytoplasm. Furthermore, recent studies demonstrated the presence of so-called progenitor cells of ICC, similar to ICC-DMP in appearance, expressing insulin-like growth factor and CD34, indicating their stem cell nature. The author proposes that all GISTs develop from the common progenitor cells similar to primitive gut cells, which may differentiate into tumor cells with more myoid features in the stomach (similar to so-called ICC-DMP) as well as spindle cells with less myoid features (similar to ICC-MP [interstitial cells of Cajal associated with the myenteric plexus] in the small intestine and rectum). ICC-DMP have been recruited in the group of ICC by electron microscopic technique alone without methylene blue stain and it is questionable whether they are part of ICC depicted by the ICC network originally shown by Dr. Cajal more than century ago. Recent discovery of their expression of insulin-like growth factors may indicate that they represent persisting primitive gut cells (gut stem cells), which may serve as the progenitor cells to GIST. It is also pointed out that in this era of ICC and GIST pandemonium, a minority of intestinal stromal tumors with mature smooth muscle features have been totally ignored; these now appear to belong to GISTs, representing the best differentiated example among the tumors developing from the same progenitor cells.
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PMID:Gastrointestinal stromal tumor: an ultrastructural investigation on regional differences with considerations on their histogenesis. 2045 65

Interstitial cells of Cajal (ICC) generate electrical rhythmicity and transduce neural signals in the gastrointestinal musculature. ICC express the proto-oncogene c-kit, a receptor tyrosine kinase, and are identified morphologically by c-Kit immunoreactivity. The c-kit gene is allelic with the murine white-spotting locus W, and mutations of c-kit are known as W mutations. W mutations affect various developmental aspects of hematopoietic cells, germ cells, melanocytes, mast cells and ICC. We examined W(jic)/W(jic) mutant mice that have a mutation in the tyrosine kinase domain resulting in severe loss of protein function. W(jic)/W(jic) homozygotes exhibited white coats and black eyes. The gross morphology of the gastrointestinal tract showed no abnormality in mutant mice other than a forestomach papilloma. In the stomach, intramuscular ICC (ICC-IM) were missing, and myenteric ICC (ICC-MY) were reduced in number. In the small intestine, the number of ICC-MY was severely reduced; however there was a normal distribution of deep muscular plexus ICC (ICC-DMP). In the cecum, the numbers of ICC-IM and ICC-MY were severely depleted. ICC-IM were almost entirely absent in the colon, whereas ICC-MY loss was restricted to the distal colon. Patterns of ICC deficiency were generally similar between W(jic)/W(jic) mice and W/W(v) mutants, which lack a specific type of ICC. The enteric nervous system of the mutant mice appeared normal. From these findings, we conclude that W(jic)/W(jic) mice represent a distinct, novel genotype resulting in a lack of a specific type of ICC in the gastrointestinal musculature.
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PMID:Interstitial cells of Cajal in the gastrointestinal musculature of W(jic) c-kit mutant mice. 2197 9

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