Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The W locus of mice encodes the c-kit receptor tyrosine kinase. Recently, we characterized a novel mutant allele, Wn, and demonstrated that the c-kit protein synthesized in Wn/Wn cultured mast cells (CMC) was reduced in size and not expressed on their surface (Tsujimura et al., 1993). In this study, we further examined biochemical nature of the mutant form of c-kit protein, by using Wn/Wn CMC and 293T cells transfected with Wn-type c-kit cDNA (c-kitWn). The c-kit product synthesized in Wn/Wn CMC was truncated almost all cytoplasmic domain and was less glycosylated. In c-kitWn-transected cells, both glycosylation and extracellular expression of c-kit protein was also impaired, however, no truncation was detected. These results indicate that Wn-mutant form of c-kit product is insufficient in maturation, which is associated with impairments in the transport to the plasma membrane, and retention of the mutant protein in endoplasmic reticulum is suggested. This is the first demonstration of the c-kit mutation affecting posttranslational processing its product.
 ...
PMID:Wn mutation of c-kit receptor affects its post-translational processing and extracellular expression. 750

Observation of whole mount stretch preparations using the zinc-iodide-osmic acid method reveals a wide variety of interstitial cells in different tissue layers of the guinea-pig small intestine. And a subsequent electron-microscopic examination and survey of references makes clear that the interstitial cells of Cajal (ICC) depicted in original drawings of Cajal are heterogeneous and correspond to different types of interstitial cells. The myenteric ICC are characterized by long dichotomous branching processes which constitute cellular networks independent from the nerve plexus and form many gap junctions at their tips. Their ultrastructure is similar to that of fibroblasts and they have no basal lamina. The myenteric ICC show strong immunoreactivity for vimentin and the c-kit receptor, and probably correspond to the intestinal pacemaker cells. Within the circular muscle layer, ICC are represented by the cells that are closely associated with fine nerve bundles. The ICC have various shapes, ranging from bipolar to stellate, depending on the running pattern of the nerve fibers that they are associated with. They show fibroblast-like ultrastructure and have no basal lamina. They form gap junctions with smooth muscle cells and are immunoreactive for vimentin. On the other hand, ICC associated with the deep muscular plexus described in the guinea-pig by Cajal could not be clearly identified. However, it is suggested that the ICC in this location may correspond to glycogen-rich cells possessing a basal lamina. Although they show a fairly well-developed rough endoplasmic reticulum, Golgi apparatus and immunoreactivity for vimentin, ICC of the deep muscular plexus are probably specialized smooth muscle cells in nature.
 ...
PMID:Identification of the interstitial cells of Cajal. 883 65

Interstitial cells in the circular muscle layer of the stomach of the Ws/Ws mutant rat, which lacks c-kit-expressing cells, and its siblings have been studied by electron microscopy. In the sibling control rats, two types of interstitial cells are found lying in close association with nerve bundles. Cells of the first type are characterized by electron-dense cytoplasm containing abundant mitochondria, granular endoplasmic reticulum, and Golgi apparatus. Intermediate filaments are richly distributed throughout the perinuclear region and the cell processes. Caveolae, subsurface cisterns, and indistinct basal lamina are observed along the cell membrane. The most conspicuous feature of this cell type is the existence of many large gap junctions that interconnect with the same type of cell, smooth muscle cells, or cells of the second type. Cells of the second type show an ultrastructure similar to fibroblasts, viz., a well-developed Golgi apparatus and granular endoplasmic reticulum whose cisterns often show a dilated form and contain flocculent material. Unlike typical fibroblasts, however, cells of this type also form many gap junctions with cells of the first type and smooth muscle cells. Both types of cells are observed in close apposition to nerve varicosities. Since cells of the first type are absent in the Ws/Ws mutant rat, we concluded that they correspond to c-kit-expressing cells and to interstitial cells of Cajal.
 ...
PMID:Ultrastructural identification of the c-kit-expressing interstitial cells in the rat stomach: a comparison of control and Ws/Ws mutant rats. 918 8

c-Kit immunopositive cells are considered to be pacemakers and/or mediators of neurotransmission in the gastrointestinal tract. They also correspond to the interstitial cells of Cajal (ICs) in mice. The normal distribution of c-Kit positive cells and their relation to ICs in the human gastrointestinal tract remain unclear. In this study we examine the distribution of c-Kit positive cells and their ultrastructure in normal human tissue. We then classified them and examined their relationship to ICs. Thirty nine samples of gut from the esophagus to the sigmoid colon from humans (ranging in age from a 16 week old fetus to a 57 year old and without motility disorders), were processed for immunohistochemistry, electronmicroscopy and immuno-electronmicroscopy. c-Kit immunopositive cells were located in the external muscle from the lower esophagus to the sigmoid colon, wherever the external muscle was composed of smooth muscle cells, and they were classified morphologically into two groups. Cells in the first group were mainly spindle-shaped bipolar cells with few branches; these cells ran parallel to nearby smooth muscle. Ultrastructurally, they possessed many intermediate filaments and caveolae. The spindle-shaped cells were present in the esophagus, stomach and small intestine. The second group of cells were located only in the colon, and were multipolar or bipolar cells with numerous branches. Cells in the second group were also rich in caveolae and/or smooth endoplasmic reticulum, but intermediate filaments were not prominent. Although both groups of c-Kit immunopositive cells corresponded to ICs, some ICs in the human gut do not appear to express c-Kit immunoreactivity.
 ...
PMID:c-Kit immunoreactive interstitial cells in the human gastrointestinal tract. 993 68

The ultrastructure of the wild-type (+/+) mice small intestine was compared with c-kit mutant (W/W(nu)) mice which only have few interstitial cells of Cajal (ICC) associated with Auerbach's plexus, in order to elucidate whether the specialized membrane contacts are general features of so-called fibroblast-like cells that are widely distributed in the tunica muscularis of the alimentary tract. Fibroblast-like cells in the Auerbach region were found in approximately equal number in W/W(nu) mice as in +/+ mice, while ICC associated with Auerbach's plexus (ICC-AP) could not be demonstrated in W/W(nu) mice in the present investigation. Fibroblast-like cells were characterized by cytoplasm of moderate to high electron density, well developed rough endoplasmic reticulum and nuclei with thick peripheral accumulations of heterochromatin. There were no basal lamina and caveolae along the cell membrane. It was observed that single fibroblast-like cells formed probable small gap junctions with muscle cells of both circular and longitudinal layers. Fibroblast-like cells with the same features were also observed in the region of the deep muscular plexus in both +/+ and W/W(nu) mice. The present observation, together with our previous studies on rats and guinea-pigs, suggest the common presence of gap junctions or gap junction-like structures on fibroblast-like cells in the gastrointestinal musculature and their involvement in the regulatory system of gastrointestinal motility by passing electrical or molecular signals to influence the state of muscle tonus.
 ...
PMID:Ultrastructural observations of fibroblast-like cells forming gap junctions in the W/W(nu) mouse small intestine. 1078 80

The role of interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP) in the pathophysiology of inflammation-induced abnormalities in gut motor activity is poorly understood. Therefore we applied a well-described model of inflammation (infection by Trichinella spiralis) to the mouse small intestine where the structure and function of ICC-AP are best known. Electron microscopic evaluation revealed that 1 to 3 days after infection, selective and patchy damage to the ICC processes occurred, thereby disrupting contacts between these ICC and smooth muscle cells as well as ICC and nerves, which was associated with disordered electrical activity and abnormal peristalsis. Ten to 15 days after infection, damage to ICC-AP was maximal and now involving the cell body and major processes. Marked synthetic activity and regrowth of their processes occurred from day 3 onward and recovery was completed at day 40 after infection. No changes to the network of ICC-AP were seen with c-Kit immunohistochemistry. From day 1 after infection, macrophages infiltrated the AP area, making close contact including peg-and-socket-like junctions with smooth muscle cells and ICC-AP but up to day 6 after infection without any sign of phagocytosis. By day 6 after infection, lymphocytes entered the musculature forming close contacts with ICC-AP. This was not associated with damage to ICC-AP but with proliferation of rough endoplasmic reticulum. From day 23 onward, immune cells withdrew from the musculature except macrophages, resulting in a markedly increased population of macrophages in the AP area at day 60 after infection.
 ...
PMID:Pathology of interstitial cells of Cajal in relation to inflammation revealed by ultrastructure but not immunohistochemistry. 1194 37

At least two populations of c-kit positive interstitial cells of Cajal (ICC) lie in the gastric wall, one located at the myenteric plexus level has a pace-making function and the other located intramuscularly is intermediary in the neurotransmission and regenerates the slow waves. Both of these ICC sub-types express full-length dystrophin. Mdx mice, an animal model lacking in full-length dystrophin and used to study Duchenne muscular dystrophy (DMD), show gastric dismotilities. The aim of the present study was to verify in mdx mice whether: (i) gastric ICC undergo morphological changes, through immunohistochemical and ultrastructural analyses; and (ii) there are alterations in the electrical activity, using intracellular recording technique. In control mice, ICC sub-types showed heterogeneous ultrastructural features, either intramuscularly or at the myenteric plexus level. In mdx mice, all of the ICC sub-types underwent important changes: coated vesicles were significantly more numerous and caveolae significantly fewer than in control; moreover, cytoskeleton and smooth endoplasmic reticulum were reduced and mitochondria enlarged. c-Kit-positivity and integrity of the ICC networks were maintained. In the circular muscle of normal mice slow waves, which consisted of initial and secondary components, occurred with a regular frequency. In mdx mice, slow waves occurred in a highly dysrhythmic fashion and they lacked a secondary component. We conclude that the lack of the full-length dystrophin is associated with ultrastructural modifications of gastric ICC, most of which can be interpreted as signs of new membrane formation and altered Ca(2+) handling, and with defective generation and regeneration of slow wave activity.
 ...
PMID:Ultrastructural changes in the interstitial cells of Cajal and gastric dysrhythmias in mice lacking full-length dystrophin (mdx mice). 1504 12

Previous reports describing Cajal-like interstitial cells in human uterus are contradictory in terms of c-kit immunoreactivity: either negative (but vimentin-positive) in pregnant myometrium, or positive, presumably in the endometrium. The aim of this study was to verify the existence of human myometrial Cajal-like interstitial cells (m-CLIC). Six different, complementary approaches were used: 1) methylene-blue supravital staining of tissue samples (cryosections), 2) methylene blue and Janus green B vital staining (m-CLIC and mitochondrial markers, respectively), and 3) extracellular single-unit electrophysiological recordings in cell cultures, 4) non-conventional light microscopy on glutaraldehyde/osmium fixed, Epon-embedded semi-thin sections (less than 1 microm) stained with toluidine blue (TSM), 5) transmission electron microscopy (TEM), and 6) immunofluorescence (IF). We found m-CLIC in myometrial cryosections and in cell cultures. In vitro, m-CLIC represented approximately 7% of the total cell number. m-CLIC had 2-3 characteristic processes which were very long (approximately 60 microm), very thin (< or =0.5 microm) and moniliform. The dilated portions of processes usually accommodated mitochondria. In vitro, m-CLIC exhibited spontaneous electrical activity (62.4+/-7.22 mV membrane potentials, short duration: 1.197+/-0.04 ms). Moreover, m-CLIC fulfilled the usual TEM criteria, the so-called 'gold' or 'platinum' standards (e.g. the presence of discontinuous basal lamina, caveolae, endoplasmic reticulum, and close contacts between each other, with myocytes, nerve fibers and/or capillaries etc.). IF showed that m-CLIC express CD117/c-kit, sometimes associated with CD34, with vimentin along their processes. In conclusion, we describe myometrial Cajal-like interstitial cells that have affinity for methylene blue and Janus green B vital dyes, fulfill (all) TEM criteria, express CD117/c-kit and have spontaneous electric activity.
 ...
PMID:C-kit immunopositive interstitial cells (Cajal-type) in human myometrium. 1596 60

We have previously shown the existence of ICLC in human resting mammary gland stroma by means of methylene blue (vital) staining and c-kit immunopositivity (immunofluorescence and immunohistochemistry). In addition, we reported the phenotype characteristics of these ICLC in vitro (primary cell cultures). Since the identification of ICLC outside the gut requires, at this moment, the obligatory use of TEM, we used this technique and provide unequivocal evidence for the presence of ICLC in the intralobular stroma of human resting mammary gland. According to the 'platinum standard' (10 TEM criteria for the certitude diagnosis of ICLC), we found interstitial cells with the following characteristics: 1. location: among the tubulo-alveolar structures, in the non-epithelial space; 2. caveolae: approximately 2.5% of cell volume; 3. mitochondria: approximately 10% of cell volume; 4. endoplasmic reticulum: either smooth or rough, approximately 2-3% of cell volume; 5. cytoskeleton: intermediate and thin filaments, as well as microtubules are present; 6. myosin thick filaments: undetectable; 7. basal lamina: occasionally found; 8. gap junctions: occasionally found; 9. close contacts with targets: nerve fibers, capillaries, immunoreactive cells by 'stromal synapses'; 10. characteristic cytoplasmic processes: i) number: frequently 2-3; ii) length: several tens of mum; iii) thickness: uneven caliber, 0.1-0.5 microm, with dilations, but very thin from the emerging point; iv) aspect: moniliform, usually with mitochondria located in dilations; v) branching: dichotomous pattern; vi) Ca(2+) release units: are present; vii) network labyrinthic system: overlapping cytoplasmic processes. It remains to be established which of the possible roles that we previously suggested for ICLC (e.g. juxta- and/or paracrine secretion, uncommited progenitor cells, immunological surveillance, intercellular signaling, etc.) are essential for the epithelium/stroma equilibrium in the mammary gland under normal or pathological conditions.
 ...
PMID:Interstitial Cajal-like cells (ICLC) in human resting mammary gland stroma. Transmission electron microscope (TEM) identification. 1636 98

We have previously reported (Hinescu & Popescu, 2005) the existence of interstitial Cajal-like cells (ICLC), by transmission electron microscopy, in human atrial myocardium. In the present study, ICLC were identified with non-conventional light microscopy (NCLM) on semi-thin sections stained with toluidine blue and immunohistochemistry (IHC) for CD117/c-kit, CD34, vimentin and other additional antigens for differential diagnosis. Quantitatively, on semi-thin sections, ICLC represent about 1-1.5% of the atrial myocardial volume (vs. approximately 45% working myocytes, approximately 2% endothelial cells, 3-4% for other interstitial cells, and the remaining percentage: extracellular matrix). Roughly, there is one ICLC for 8-10 working atrial myocytes in the intercellular space, beneath the epicardium, with a characteristic (pyriform, spindle or triangular) shape. These ICLC usually have 2-3 definitory processes, emerging from cell body, which usually embrace atrial myocytes (260 nm average distance plasmalemma/sarcolemma) or establish close contact with nerve fibers or capillaries (approximately 420 nm average distance to endothelial cells). Cell prolongations are characteristic: very thin (mean thickness = 0.15+/-0.1 microm), very long for a non-nervous cell (several tens of microm) and moniliform (uneven caliber). Stromal synapses between ICLC and other interstitial cells (macrophages) were found (e.g. in a multicontact type synapse, the average synaptic cleft was approximately 65 nm). Naturally, the usual cell organelles (mitochondria, smooth and rough endoplasmic reticulum, intermediate filaments) are relatively well developed. Caveolae were also visible on cell prolongations. No thick filaments were detected. IHC showed that ICLC were slightly and inconsistently positive for CD117/c-kit, variously co-expressed CD34 and EGF receptor, but appeared strongly positive for vimentin, along their prolongations. Some ICLC seemed positive for a-smooth muscle actin and tau protein, but were negative for nestin, desmin, CD13 and S-100. In conclusion, we provide further evidence of the existence of ICLC in human atrial myocardium, supporting the possible ICLC role in pacemaking, secretion (juxta- and/or paracrine), intercellular signaling (neurons and myocytes). For pathology, ICLC might as well be 'players' in arrhythmogenesis and atrial remodeling.
 ...
PMID:Interstitial Cajal-like cells (ICLC) in atrial myocardium: ultrastructural and immunohistochemical characterization. 1656 37


1 2 3 Next >>