The Genomic Organization of a Human Creatine Transporter (CRTR) Gene Located in Xq28

Sandoval, Natalia; Bauer, Dierk; Brenner, Volker; Coy, Johannes F.; Drescher, Bernd; Kioschis, Petra; Korn, Bernd; Nyakatura, Gerald; Poustka, Annemarie; Reichwald, Kathrin; Rosenthal, André; Platzer, Matthias

doi:10.1006/geno.1996.0373

Cited by 30 publications

(14 citation statements)

References 5 publications

(3 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Only one of the eight duplicates, in this study, involved the transposition of a complete genic region (all introns and exons as well as putative promoter region of the creatine transporter gene from Xq28). Transcribed cDNAs have been identified and characterized for both the Xq28 and 16p11.2 paralogs (SCL6A8 and SCL6A10) (Iyer et al 1996;Sandoval et al 1996). Interestingly, the ancestral Xq28 copy (Eichler et al 1996) is expressed in all tissue types, whereas transcription of the chromosome 16 paralogous creatine transporter gene is restricted in humans to the testis.…”

Section: Genome Research 1053mentioning

confidence: 99%

CAGGG Repeats and the Pericentromeric Duplication of the Hominoid Genome

Eichler¹,

Archidiacono²,

Rocchi³

1999

Genome Res.

View full text Add to dashboard Cite

Gene duplication is one of the primary forces of evolutionary change. We present data from three different pericentromeric regions of human chromosomes, which indicate that such regions of the genome have been sites of recent genomic duplication. This form of duplication has involved the evolutionary movement of segments of genomic material, including both intronic and exonic sequence, from diverse regions of the genome toward the pericentromeric regions. Sequence analyses of the target sites of duplication have identified a novel class of interspersed GC-rich repeats located precisely at the boundaries of duplication. Estimates of the evolutionary age of these duplications indicate that they have occurred between 10 and 25 mya. In contrast, comparative analyses confirm that the GC-rich pericentromeric repeats have existed within the pericentromeric regions of primate chromosomes before the divergence of the cercopithecoid and hominoid lineages (∼30 mya). These data provide molecular evidence for considerable interchromosomal duplication of genic segments during the evolution of the hominoid genome and strongly implicate GC-rich repeat elements as playing a direct role in the pericentromeric localization of these events Genome evolution is dependent on the processes of single-base-pair mutation and gene duplication. Duplication of a gene followed by mutation is responsible for the emergence of new genes with specialized functions in an evolving species. Two distinct molecular mechanisms of gene duplication are generally recognized. Tandem duplication of an ancestral gene, vis-à-vis processes of unequal crossover, produces a clustered family of related genes (Smith 1976). In contrast, whole-genome duplication (polyploidy) followed by chromosomal rearrangement and the re-establishment of the disomic state has been proposed as a mechanism for the interchromosomal duplication of large segments of a genome (Ohno 1970). The latter model, put forward originally by Susumu Ohno, explains observations of conserved genic synteny among nonhomologous chromosomes. Because of the genetic consequences of polyploidy, such events, although important in the early expansion of eukaryotic genomes, are rare and ancient (Ohno 1993;Wolfe and Shields 1997). Within the vertebrate lineage, for example, the last tetraploidization event leading to genome duplication is estimated to have occurred >400 mya (Lundin 1993). If polyploidy were the only model by which entire genes could be duplicated among nonhomologous chromosomes, it would then follow that interchromosomal paralogs of recent origin would be unexpected.Recent analyses of data from the Human Genome Project suggest a third form of genomic duplication, which is mechanistically distinct from polyploidy and tandem duplication models of genome evolution. Several independent reports indicate that genic segments, ranging in length from 5 kb to 30 kb, possess duplicate copies within the pericentromeric regions of human autosomes (Borden et

show abstract

Section: Genome Research 1053mentioning

confidence: 99%

CAGGG Repeats and the Pericentromeric Duplication of the Hominoid Genome

Eichler¹,

Archidiacono²,

Rocchi³

1999

Genome Res.

View full text Add to dashboard Cite

show abstract

“…cDNA and gene sequencing of the CRTs from rabbit, rat, mouse, human, and the electric ray (Torpedo) (5)(6)(7)(8)(9)(10) have shown that CRTs are composed of 611-636 amino acid residues with a calculated molecular mass of ϳ70 kDa. The CRT sequences (Protein Data Bank accession number for rat CRT ϭ P28570 and for human CRT ϭ P48029) are most closely related to the ␥-aminobutyric acid, taurine/betaine transporter subfamily (46 -53% amino acid sequence identity), while the homology to the glycine, proline, catecholamine, and serotonin transporters is less pronounced (38 -34%).…”

mentioning

confidence: 99%

Novel Mitochondrial Creatine Transport Activity

Walzel¹,

Speer²,

Zanolla³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Immunoblotting of isolated mitochondria from rat heart, liver, kidney, and brain with antibodies made against N-and C-terminal peptide sequences of the creatine transporter, together with in situ immunofluorescence staining and immunogold electron microscopy of adult rat myocardium, revealed two highly related polypeptides with molecular masses of ϳ70 and ϳ55 kDa in mitochondria. These polypeptides were localized by immunoblotting of inner and outer mitochondrial membrane fractions, as well as by immunogold labeling in the mitochondrial inner membrane. In addition, a novel creatine uptake via a mitochondrial creatine transport activity was demonstrated by [ 14 C]creatine uptake studies with isolated mitochondria from rat liver, heart, and kidney showing a saturable low affinity creatine transporter, which was largely inhibited in a concentrationdependent manner by the sulfhydryl-modifying reagent NEM, as well as by the addition of the above anti-creatine transporter antibodies to partially permeabilized mitochondria. Mitochondrial creatine transport was to a significant part dependent on the energetic state of mitochondria and was inhibited by arginine, and to some extent also by lysine, but not by other creatine analogues and related compounds. The existence of an active creatine uptake mechanism in mitochondria indicates that not only creatine kinase isoenzymes, but also creatine transporters and thus a certain proportion of the creatine kinase substrates, might be subcellularly compartmentalized. Our data suggest that mitochondria, shown here to possess creatine transport activity, may harbor such a creatine/phosphocreatine pool.

show abstract

“…There are several abbreviations for the creatine transporter gene, its mRNA and its protein; SLC6A8 (NGNC guidelines official name), CT1 (Iyer et al, 1996), CRT (Sora et al, 1994), CreaT (Nash et al, 1994), and CRTR (Sandoval et al, 1996). To prevent confusion between the different splice variants and the paralogous gene on chromosome 16 (SLC6A10), we named the splice variants in a more logical way, using SLC6A8 for the mRNA encoding the known full-length creatine transporter protein and reserving SLC6A8A for this mRNA.…”

Section: Discussionmentioning

confidence: 99%