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801.
Diekman AB 《Cellular and molecular life sciences : CMLS》2003,60(2):298-308
Glycoconjugates in the mammalian reproductive tract are critical components of the molecular mechanisms that control sperm
maturation, sperm transport and gamete interactions. In the oviduct of many species, sperm transport and maturation are regulated
by protein-carbohydrate interactions that form a sperm reservoir. Subsequently, gamete interactions are mediated by the binding
of lectin-like sperm proteins with carbohydrate moieties on the zona pellucida. The sperm glycocalyx is extensively modified
during sperm transport and maturation. Multiple functions have been proposed for this dense carbohydrate layer overlying the
sperm plasmalemma, and sperm-surface carbohydrates have been implicated in immune-mediated human infertility. The structure
and function of glycoconjugates in the oviductal sperm reservoir, the zona pellucida, and on the sperm surface are reviewed. 相似文献
802.
Human mitochondrial tRNAs in health and disease 总被引:6,自引:0,他引:6
Florentz C Sohm B Tryoen-Tóth P Pütz J Sissler M 《Cellular and molecular life sciences : CMLS》2003,60(7):1356-1375
The human mitochondrial genome encodes 13 proteins, all subunits of the respiratory chain
complexes and thus involved in energy metabolism. These genes are translated by 22 transfer RNAs
(tRNAs), also encoded by the mitochondrial genome, which form the minimal set required for reading
all codons. Human mitochondrial tRNAs gained interest with the rapid discovery of correlations
between point mutations in their genes and various neuromuscular and neurodegenerative disorders.
In this review, emerging fundamental knowledge on the structure/function relationships of these
particular tRNAs and an overview of the large variety of mechanisms within translation, affected by
mutations, are summarized. Also, initial results on wide-ranging molecular consequences of mutations
outside the frame of mitochondrial translation are highlighted. While knowledge of mitochondrial
tRNAs in both health and disease increases, deciphering the intricate network of events leading
different genotypes to the variety of phenotypes requires further investigation using adapted
model systems.Received 3 December 2002; received after revision 14 January 2003; accepted 27 January 2003 相似文献
803.
804.
Rawat UB Zavialov AV Sengupta J Valle M Grassucci RA Linde J Vestergaard B Ehrenberg M Frank J 《Nature》2003,421(6918):87-90
Protein synthesis takes place on the ribosome, where genetic information carried by messenger RNA is translated into a sequence of amino acids. This process is terminated when a stop codon moves into the ribosomal decoding centre (DC) and is recognized by a class-1 release factor (RF). RFs have a conserved GGQ amino-acid motif, which is crucial for peptide release and is believed to interact directly with the peptidyl-transferase centre (PTC) of the 50S ribosomal subunit. Another conserved motif of RFs (SPF in RF2) has been proposed to interact directly with stop codons in the DC of the 30S subunit. The distance between the DC and PTC is approximately 73 A. However, in the X-ray structure of RF2, SPF and GGQ are only 23 A apart, indicating that they cannot be at DC and PTC simultaneously. Here we show that RF2 is in an open conformation when bound to the ribosome, allowing GGQ to reach the PTC while still allowing SPF-stop-codon interaction. The results indicate new interpretations of accuracy in termination, and have implications for how the presence of a stop codon in the DC is signalled to PTC. 相似文献
805.
806.
Floyd JA Gold DA Concepcion D Poon TH Wang X Keithley E Chen D Ward EJ Chinn SB Friedman RA Yu HT Moriwaki K Shiroishi T Hamilton BA 《Nature genetics》2003,35(3):221-228
Endogenous retroviruses have shaped the evolution of mammalian genomes. Host genes that control the effects of retrovirus insertions are therefore of great interest. The modifier-of-vibrator-1 locus (Mvb1) controls levels of correctly processed mRNA from genes mutated by endogenous retrovirus insertions into introns, including the Pitpn(vb) tremor mutation and the Eya1(BOR) model of human branchiootorenal syndrome. Positional complementation cloning identifies Mvb1 as the nuclear export factor Nxf1, providing an unexpected link between the mRNA export receptor and pre-mRNA processing. Population structure of the suppressive allele in wild Mus musculus castaneus suggests selective advantage. A congenic Mvb1(CAST) allele is a useful tool for modifying gene expression from existing mutations and could be used to manipulate engineered mutations containing retroviral elements. 相似文献
807.
808.
Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia 总被引:3,自引:0,他引:3
Pollock PM Cohen-Solal K Sood R Namkoong J Martino JJ Koganti A Zhu H Robbins C Makalowska I Shin SS Marin Y Roberts KG Yudt LM Chen A Cheng J Incao A Pinkett HW Graham CL Dunn K Crespo-Carbone SM Mackason KR Ryan KB Sinsimer D Goydos J Reuhl KR Eckhaus M Meltzer PS Pavan WJ Trent JM Chen S 《Nature genetics》2003,34(1):108-112
809.
Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity 总被引:13,自引:0,他引:13
Neuropathy target esterase (NTE) is involved in neural development and is the target for neurodegeneration induced by selected organophosphorus pesticides and chemical warfare agents. We generated mice with disruptions in Nte, the gene encoding NTE. Nte(-/-) mice die after embryonic day 8, and Nte(+/-) mice have lower activity of Nte in the brain and higher mortality when exposed to the Nte-inhibiting compound ethyl octylphosphonofluoridate (EOPF) than do wild-type mice. Nte(+/-) and wild-type mice treated with 1 mg per kg of body weight of EOPF have elevated motor activity, showing that even minor reduction of Nte activity leads to hyperactivity. These studies show that genetic or chemical reduction of Nte activity results in a neurological phenotype of hyperactivity in mammals and indicate that EOPF toxicity occurs directly through inhibition of Nte without the requirement for Nte gain of function or aging. 相似文献
810.
Burgay M D'Amico N Possenti A Manchester RN Lyne AG Joshi BC McLaughlin MA Kramer M Sarkissian JM Camilo F Kalogera V Kim C Lorimer DR 《Nature》2003,426(6966):531-533
The merger of close binary systems containing two neutron stars should produce a burst of gravitational waves, as predicted by the theory of general relativity. A reliable estimate of the double-neutron-star merger rate in the Galaxy is crucial in order to predict whether current gravity wave detectors will be successful in detecting such bursts. Present estimates of this rate are rather low, because we know of only a few double-neutron-star binaries with merger times less than the age of the Universe. Here we report the discovery of a 22-ms pulsar, PSR J0737-3039, which is a member of a highly relativistic double-neutron-star binary with an orbital period of 2.4 hours. This system will merge in about 85 Myr, a time much shorter than for any other known neutron-star binary. Together with the relatively low radio luminosity of PSR J0737-3039, this timescale implies an order-of-magnitude increase in the predicted merger rate for double-neutron-star systems in our Galaxy (and in the rest of the Universe). 相似文献