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Family Receptors (family + receptor)
Selected AbstractsImpaired behavioural flexibility and memory in mice lacking GDNF family receptor ,2EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2004Vootele Vőikar Abstract The glial cell line-derived neurotrophic factor (GDNF) family receptor GFR,2 is the binding receptor for neurturin (NRTN). The main biological responses of GFR,2 are mediated via the Ret receptor tyrosine kinase, although it may also signal independently of Ret via the neural cell adhesion molecule NCAM. GFR,2 is expressed in many neurons of both the central and peripheral nervous system. Mice lacking GFR,2 receptors do not exhibit any gross defects in the central nervous system structure. However, they display profound deficits in the parasympathetic and enteric nervous system, accompanied by significant reduction in body weight after weaning. Here we present the results of behavioural analysis of the GFR,2-knockout mice. The knockout mice did not differ from wild-type mice in basic tests of motor and exploratory activity. However, differences were established in several memory tasks. The knockout mice were not impaired in the acquisition of spatial escape strategy. However, the deficit in flexibility in establishing a new strategy was revealed during reversal learning with the platform in the opposite quadrant of the pool. Furthermore, the knockout mice displayed significant impairment in contextual fear conditioning and conditioned taste aversion tests of memory. The results suggest that GFR,2 signalling plays a role in the development or maintenance of cognitive abilities that help in solving complex learning tasks. [source] Magnetic activated cell sorting allows isolation of spermatogonia from adult primate testes and reveals distinct GFRa1-positive subpopulations in menJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2010Kathrin Gassei Abstract Background, Isolation of spermatogonial stem cells (SSCs) could enable in vitro approaches for exploration of spermatogonial physiology and therapeutic approaches for fertility preservation. SSC isolation from adult testes is difficult due to low cell numbers and lacking cell surface markers. Glial cell-derived neurotrophic factor family receptor alpha-1 (GFR,1) plays a crucial role for the maintenance of SSCs in rodents and is expressed in monkey spermatogonia. Methods, Magnetic activated cell sorting was employed for the enrichment of GFR,1+ spermatogonia from adult primate testes. Results, Magnetic activated cell sorting of monkey cells enriched GFR,1+ cells threefold. 11.4% of GFR,1+ cells were recovered. 42.9% of GFR,1+ cells were recovered in sorted fractions of human testicular cells, representing a fivefold enrichment. Interestingly, a high degree of morphological heterogeneity among the GFR,1+ cells from human testes was observed. Conclusions, Magnetic activated cell sorting using anti-GFR,1 antibodies provides an enrichment strategy for spermatogonia from monkey and human testes. [source] Translational Mini-Review Series on Immunodeficiency: Molecular defects in common variable immunodeficiencyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007C. Bacchelli Summary Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative humoral function that are heterogeneous in their immunological profile and clinical manifestations. The recent identification of four monogenic defects that result in the CVID phenotype also demonstrates that the genetic basis of CVID is highly variable. Mutations in the genes encoding the tumour necrosis factor (TNF) superfamily receptors transmembrane activator and calcium-modulating ligand interactor (TACI) and B cell activation factor of the TNF family receptor (BAFF-R), CD19 and the co-stimulatory molecule inducible co-stimulator molecule (ICOS) all lead to CVID and illustrate the complex interplay required to co-ordinate an effective humoral immune response. The molecular mechanisms leading to the immune defect are still not understood clearly and particularly in the case of TACI, where a number of heterozygous mutations have been found in affected individuals, the molecular pathogenesis of disease requires further elucidation. Together these defects account for perhaps 10,15% of all cases of CVID and it is highly likely that further genetic defects will be identified. [source] Sequential activation of Notch family receptors during mouse spermatogenesisDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 1 2003Shintaro Mori The expression pattern of Notch family receptors during mouse spermatogenesis was examined by immunohistochemistry. The entire cytoplasm of spermatogonia, spermatocytes and spermatids showed staining with antibodies against extracellular domains of Notch1, 2 and 4. In contrast, the nuclei of spermatogonia showed staining with an antibody against the intracellular domain of Notch3, and the nuclei of spermatocytes and spermatids showed staining with antibodies against the intracellular domains of Notch1 and 4. During regeneration of spermatogonia in busulfan-treated mice, the nuclei of all proliferating cells showed staining for the intracellular domain of Notch3. Western blot analysis showed that the molecular weights of the intracellular domains of Notch1 and 3 localizing in the nuclear fraction were smaller than those in the cytoplasmic fraction. This was consistent with the theory that the intracellular domain of Notch was cleaved in the cytoplasm and translocated to the nucleus. These results suggest that different Notch signals are sequentially activated during mouse spermatogenesis and control the proliferation and differentiation of spermatogenic stem cells. [source] Interleukin-6 cytokine family member oncostatin M is a hair-follicle-expressed factor with hair growth inhibitory propertiesEXPERIMENTAL DERMATOLOGY, Issue 1 2008Mei Yu Abstract:, The activation of receptor complexes containing glycoprotein 130 (gp130) identifies the interleukin (IL)-6 cytokine family. We examined members of this family for their expression and activity in hair follicles. Quantitative polymerase chain reaction using mRNA derived from microdissected, anagen-stage human hair follicles and comparison to non-follicular skin epithelium revealed higher levels of IL-6 (15.5-fold) and oncostatin M (OSM, 3.4-fold) in hair follicles. In contrast, expression of all mRNAs coding for IL-6 cytokine family receptors was reduced. Immunohistology suggested expression of OSM, gp130, leukaemia inhibitory factor receptor (LIFr) and IL-11r in the hair follicle root sheaths and dermal papilla, while IL-11, IL-6r and OSMr were expressed in root sheaths alone. IL-6 was expressed in the dermal papilla while cardiotrophin-1 (CT-1) and LIF were not observed. OSM and to a lesser extent CT-1 exhibited a dose-dependent growth inhibition capacity on human hair follicles in vitro. OSM and CT-1 incubated with agarose beads and injected subcutaneously at 1 ,g per mouse into telogen skin of 65-day-old mice revealed no capacity to induce anagen hair growth. In contrast, injection of 65-day-old mice in which anagen had been induced by hair plucking revealed a moderate hair growth inhibitory capacity for OSM, but no significant effect for CT-1. The data identify OSM as a modulator of hair follicle growth and suggest other family members may also have some degree of hair growth inhibitory effect. In principle, increased expression of some IL-6 cytokine family members in cutaneous inflammation might contribute to the promotion of hair loss. [source] Molecular and cellular pathogenesis of X-linked lymphoproliferative diseaseIMMUNOLOGICAL REVIEWS, Issue 1 2005Kim E. Nichols Summary:, X-linked lymphoproliferative disease (XLP) is an inherited immune defect caused by mutations in the Src homology 2 domain-containing gene 1A, which encodes the adapter protein, signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). SAP is expressed in T cells, natural killer (NK) cells, and NKT cells, where it binds to the cytoplasmic domain of the surface receptor SLAM (CD150) and the related receptors, 2B4 (CD244), CD84, Ly9 (CD229), NK-T-B-antigen, and CD2-like receptor-activating cytotoxic T cells. SAP also binds to the Src family tyrosine kinase Fyn and recruits it to SLAM, which leads to the generation of downstream phosphotyrosine signals. While the roles of the SLAM family receptors are only beginning to be understood, experiments suggest that these molecules regulate important aspects of lymphocyte function, such as proliferation, cytokine secretion, cytotoxicity, and antibody production. Thus, in XLP patients who lack functional SAP, the SLAM family receptors may not signal properly. This property likely contributes to the phenotypes of XLP, including fulminant infectious mononucleosis, lymphoma, and hypogammaglobulinemia. Further studies of SAP and the SLAM family receptors will provide insights into XLP and elucidate the signaling events regulating lymphocyte ontogeny and function. [source] Role of 2B4-mediated signals in the pathogenesis of a murine hepatitis model independent of Fas and V,14 NKT cellsIMMUNOLOGY, Issue 1pt2 2009Hiroshi Furukawa Summary Concanavalin A (Con A)-induced hepatitis is a T-cell-mediated murine experimental model of autoimmune hepatitis. Mice lacking V,14 NKT cells were found to be less sensitive to this hepatitis and the MRL/Mp- Faslpr/lpr (MRL/lpr; i.e. Fas deficient) mice were also less sensitive. We report herein that MRL/Mp- Faslpr/lpr - Saprpl/, (MRL/lpr/rpl) mice lack V,14 NKT cells and are deficient in the Fas antigen but sensitive to Con A-induced hepatitis. The signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an adaptor molecule containing a Src homology 2 (SH2) domain. We previously reported new mutant mice found among MRL/lpr mice and revealed that SAP deficiency led to the regression of autoimmune phenotypes in mutant MRL/lpr/rpl mice. It was also revealed that CD4+ and CD8+ T cells were effector cells and that blockade of 2B4, one of the SLAM family receptors, inhibited the induction of hepatitis in MRL/lpr/rpl mice. These data suggest that signals mediated by molecules other than SAP from 2B4 in T cells played important roles in the induction of hepatitis in MRL/lpr/rpl mice. [source] Regulation of TGF-, family signaling by E3 ubiquitin ligasesCANCER SCIENCE, Issue 11 2008Yasumichi Inoue Members of the transforming growth factor-, (TGF-,) family, including TGF-,, activin and bone morphogenetic proteins (BMPs), are multifunctional proteins that regulate a wide variety of cellular responses, such as proliferation, differentiation, migration and apoptosis. Alterations in their downstream signaling pathways are associated with a range of human diseases like cancer. TGF-, family members transduce signals through membrane serine/threonine kinase receptors and intracellular Smad proteins. The ubiquitin,proteasome pathway, an evolutionarily conserved cascade, tightly regulates TGF-, family signaling. In this pathway, E3 ubiquitin ligases play a crucial role in the recognition and degradation of target proteins by the 26S proteasomes. Smad degradation regulates TGF-, family signaling; HECT (homologous to the E6-accessory protein C-terminus)-type E3 ubiquitin ligases, Smad ubiquitin regulatory factor 1 (Smurf1), Smurf2, and a RING-type E3 ubiquitin ligase, ROC1-SCFFbw1a have been implicated in Smad degradation. Smurf1 and Smurf2 bind to TGF-, family receptors via the inhibitory Smads, Smad6 and Smad7, to induce their ubiquitin-dependent degradation. Arkadia, a RING-type E3 ubiquitin ligase, induces the ubiquitination and degradation of Smad7 and corepressors, c-Ski and SnoN, to enhance TGF-, family signaling. Abnormalities in E3 ubiquitin ligases that control components of TGF-, family signaling may lead to the development and progression of various cancers. (Cancer Sci 2008; 99: 2107,2112) [source] | |||||||||||||