Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To gain a better understanding of the organization of the complex T-cell antigen receptor alpha/delta (TCR alpha/delta) locus, a deletional analysis using the known six variable (V) regions of the TCR delta was performed in informative leukemic cell lines and fresh leukemias. We and others have previously reported a high incidence of V delta 2-(D)-D delta 3 rearrangements in non-T, non-B-lymphoid precursor acute lymphocytic leukemia (LP-ALL). In contrast V delta 4, V delta 5, V delta 6 rearrangements were rare or absent. V delta-J alpha rearrangements were found in LP-ALL and in T-ALL. Our deletion and rearrangement data combined with that of others suggest the following 5' to 3' organization of the TCR alpha/delta locus: V delta 6-(V delta 4-V alpha 1.2)-V alpha 12.1-V alpha 13.1-V delta 1-V delta 17.1-V delta 5-delta Rec-V delta 2-D/J/C delta-V delta 3-TEA-psi J alpha-J alpha G. The frequency of rearrangements of the various V delta genes suggests preferential use of the V delta most proximal to D/J delta.
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PMID:Organization of the T-cell receptor delta locus by deletional analysis of acute lymphoblastic leukemias and leukemic cell lines. 183 1

Individual T cells express the CD3 molecule in association with alternative gamma delta or alpha beta heterodimeric T-cell receptors (TCRs). T-cell precursors and occasional gamma delta-expressing T cells in humans possess an unexpected 2.0-kilobase (kb) mRNA in which a tandemly repeated motif, TEA (T early alpha), has been spliced to the constant (C alpha) region. Long-range pulsed-field gel mapping as well as molecular cloning showed that TEA is located immediately 5' to the most upstream joining (J alpha) segment of the TCR alpha-chain locus. The TCR delta-chain locus is immediately 5' to TEA, and diversity (D delta) gene segments, J delta, C delta, and TEA are linked within 35 kb. The human TCR delta locus conserves a 12/23-base-pair (bp) spacer paradigm in which J delta possesses a 12-bp and V delta a 23-bp spacer, while the D delta segments have a 12 bp-D delta-23 bp spacer motif. Considerable TCR delta diversity can be generated despite the predominant use of one V delta and one J delta segment. Two D delta segments, D delta 1 and D delta 2, are 9 and 13 bp long, are frequently recombined as D delta 1-D delta 2, and reveal exonucleolytic trimming with extensive N-segment addition. A gamma delta clonal T cell possessed an effective VDDJ delta rearrangement and an intermediate DDJ delta rearrangement, arguing that the TCR delta locus displays allelic exclusion. Specific rearranging elements that delete the delta locus, delta Rec and psi J alpha, were mapped and found to separate the delta locus from the alpha locus. The delta locus including D delta 1-D delta 2-J delta 1-C delta-TEA was deleted in mature, alpha beta-expressing T cells, whereas V delta 1 was frequently retained. The location of the delta locus within the alpha locus may necessitate an exclusive choice between delta or alpha expression.
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PMID:Human T-cell antigen receptor (TCR) delta-chain locus and elements responsible for its deletion are within the TCR alpha-chain locus. 297 61

For several years, the relationship between alpha beta and gamma delta T-cell progenitors has been a topic of debate. Some argue that a subset of T-cell progenitors is "pre-committed" to the alpha beta lineage and is thus programmed to rearrange alpha, but not delta genes. It is further argued that the deletion of the delta locus by a unique rearrangement, delta rec-psi J alpha, may be the critical forerunner to V-J alpha joins in alpha beta committed cells and that a hypersensitive site (HS) termed 5'TEA might regulate such rearrangement. Here we present an alternative hypothesis. We first emphasize that directed J alpha gene rearrangements do not exclusively target the psi J alpha gene, but that clustered gene rearrangements occur throughout the J alpha locus during T-cell development. We describe the existence of not one, but at least two HS sites distributed along the J alpha locus which might serve as regulators for the gene rearrangement event. Finally, we suggest that progenitor T-cells are not committed to a particular delta or alpha gene rearrangement, but that a flexible progenitor responds to complex interactions between environmental signals and multiple regulatory elements interspersed among delta/alpha genes.
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PMID:Gene rearrangement patterning and DNase-I hypersensitive sites within the T-cell receptor J alpha locus. 789 97

The T cell receptor (TCR)-alpha and -delta loci are contained on the same chromosomal region, and yet are developmentally and genetically independent. The first element of the J alpha cluster (psi J alpha) is the site of an active rearrangement in the human thymus (delta Rec-psi J alpha rearrangement) and is localized downstream of a region expressed as a germ-line sterile transcript (TEA) in the human developing thymus. We hypothesized that the transcription of TEA could be indicative of (or responsible for) the opening of the J alpha to the V(D)J recombinase and undertook to analyze cis-acting sequences controlling the TEA transcription. The promoter of TEA was characterized. It was part of a region that is highly conserved between human and mouse and contained many sites for the putative binding of T cell-specific transcription factors. The in vitro activity of this promoter was dependent on the association with an enhancer. A strong DNase I hypersensitive site was found in the vicinity of this promoter again suggesting the possible presence of protein-DNA interactions in this region. The implications of these results in the general perspective of TCR-alpha/delta gene regulation is discussed.
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PMID:Functional characterization of the promoter for the human germ-line T cell receptor J alpha (TEA) transcript. 838 96

Electrical properties of cochlear efferent (olivocochlear) neurons were investigated with the use of the whole cell patch recording technique in slice preparations of the neonatal rat (postnatal days 5-11). Lateral and medial olivocochlear (LOC and MOC, respectively) neurons were retrogradely labeled with a fluorescent tracer injected into the cochlea. Stained neurons were identified under a fluorescence microscope, and they were subjected to whole cell recording. LOC and MOC neurons showed different electrophysiological properties. Both showed spike trains of tonic pattern in response to injection of depolarizing current pulses at the resting membrane potential (-60 to -70 mV). However, when the membrane was slightly hyperpolarized (-72 to -76 mV), LOC neurons showed spike trains with a long first interspike interval (ISI), whereas MOC neurons showed spike trains with a long latency to the first spike. Extracellular application of 4-aminopyridine (4-AP; 0.5-2 mM) shortened these ISIs and latencies. In voltage-clamp experiments, two transient outward currents with different (fast and slow) decay kinetics were observed in LOC neurons. The fast outward current (I(A-LOC)) was inactivated by the preceding depolarization, and decayed with a time constant (tau) of 86 ms (at 0 mV). The preceding potential, which reduced the current size to the half-maximum (V1/2), was -72 mV. The slow current (I(KD)) decayed with a tau of 853 ms (at 0 mV). I(A-LOC) was sensitive to 4-AP (2 mM), and was less sensitive to tetraethylammonium chloride (TEA; 20 mM). I(KD) was partially blocked by TEA (20 mM), but was insensitive to 4-AP (2 mM). The recovery from inactivation of I(A-LOC) was time dependent with a time constant (tau(rec)) of 32 ms at -90 mV. MOC neurons also showed a transient outward current that consisted of a single transient component (I(A-MOC)) with a steady outward current. I(A-MOC) was inactivated by the preceding depolarization. Decay tau of I(A-MOC) was 33 ms (at 0 mV), and V1/2 was -75 mV. I(A-MOC) was sensitive to 4-AP (0.5-1 mM). The time-dependent recovery from inactivation of I(A-MOC) was faster than that of I(A-LOC), and tau(rec) was 15 ms at -90 mV. The different kinetics of transient outward currents between LOC and MOC neurons seems to be responsible for the difference in firing properties of these two neurons.
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PMID:Lateral and medial olivocochlear neurons have distinct electrophysiological properties in the rat brain slice. 916 93