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971.
Nuclear transport mechanisms 总被引:7,自引:0,他引:7
The term nuclear transport, refers to the movement of a large variety of macromolecules both into and out of the nucleus. Transport must be extremely selective, yet also very efficient. A single type of channel, the nuclear pore complex, mediates all movement across the nuclear envelope. Selectivity is achieved through the use of families of soluble factors that target substrates for import and export and deliver them to their appropriate intracellular destinations. We now have a fairly detailed understanding of the basic mechanisms of protein import into the nucleus. Many of these same principles can be applied to protein export and perhaps RNA export. This review will summarize the current status of what is known about various transport pathways and highlight the questions that remain to be answered. 相似文献
972.
B S Mankoo N S Collins P Ashby E Grigorieva L H Pevny A Candia C V Wright P W Rigby V Pachnis 《Nature》1999,400(6739):69-73
The skeletal muscles of the limbs develop from myogenic progenitors that originate in the paraxial mesoderm and migrate into the limb-bud mesenchyme. Among the genes known to be important for muscle development in mammalian embryos are those encoding the basic helix-loop-helix (bHLH) myogenic regulatory factors (MRFs; MyoD, Myf5, myogenin and MRF4) and Pax3, a paired-type homeobox gene that is critical for the development of limb musculature. Mox1 and Mox2 are closely related homeobox genes that are expressed in overlapping patterns in the paraxial mesoderm and its derivatives. Here we show that mice homozygous for a null mutation of Mox2 have a developmental defect of the limb musculature, characterized by an overall reduction in muscle mass and elimination of specific muscles. Mox2 is not needed for the migration of myogenic precursors into the limb bud, but it is essential for normal appendicular muscle formation and for the normal regulation of myogenic genes, as demonstrated by the downregulation of Pax3 and Myf5 but not MyoD in Mox2-deficient limb buds. Our findings show that the MOX2 homeoprotein is an important regulator of vertebrate limb myogenesis. 相似文献
973.
A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy. 总被引:14,自引:0,他引:14
E M Stone A J Lotery F L Munier E Héon B Piguet R H Guymer K Vandenburgh P Cousin D Nishimura R E Swiderski G Silvestri D A Mackey G S Hageman A C Bird V C Sheffield D F Schorderet 《Nature genetics》1999,22(2):199-202
Malattia Leventinese (ML) and Doyne honeycomb retinal dystrophy (DHRD) refer to two autosomal dominant diseases characterized by yellow-white deposits known as drusen that accumulate beneath the retinal pigment epithelium (RPE). Both loci were mapped to chromosome 2p16-21 (refs 5,6) and this genetic interval has been subsequently narrowed. The importance of these diseases is due in large part to their close phenotypic similarity to age-related macular degeneration (AMD), a disorder with a strong genetic component that accounts for approximately 50% of registered blindness in the Western world. Just as in ML and DHRD, the early hallmark of AMD is the presence of drusen. Here we use a combination of positional and candidate gene methods to identify a single non-conservative mutation (Arg345Trp) in the gene EFEMP1 (for EGF-containing fibrillin-like extracellular matrix protein 1) in all families studied. This change was not present in 477 control individuals or in 494 patients with age-related macular degeneration. Identification of this mutation may aid in the development of an animal model for drusen, as well as in the identification of other genes involved in human macular degeneration. 相似文献
974.
Nucleosome mobilization catalysed by the yeast SWI/SNF complex. 总被引:18,自引:0,他引:18
975.
Auditory collusion and a coupled couple of outer hair cells. 总被引:7,自引:0,他引:7
The discrepancies between measured frequency responses of the basilar membrane in the inner ear and the frequency tuning found in psychophysical experiments led to Bekesy's idea of lateral inhibition in the auditory nervous system. We now know that basilar membrane tuning can account for neural tuning, and that sharpening of the passive travelling wave depends on the mechanical activity of outer hair cells (OHCs)3, but the mechanism by which OHCs enhance tuning remains unclear. OHCs generate voltage-dependent length changes at acoustic rates, which deform the cochlear partition. Here we use an electrical correlate of OHC mechanical activity, the motility-related gating current, to investigate mechano-electrical interactions among adjacent OHCs. We show that the motility caused by voltage stimulation of one cell in a group evokes gating currents in adjacent OHCs. The resulting polarization in adjacent cells is opposite to that within the stimulated cell, which may be indicative of lateral inhibition. Also such interactions promote distortion and suppression in the electrical and, consequently, the mechanical activity of OHCs. Lateral interactions may provide a basis for enhanced frequency selectivity in the basilar membrane of mammals. 相似文献
976.
Detection of a cystic fibrosis modifier locus for meconium ileus on human chromosome 19q13. 总被引:14,自引:0,他引:14
977.
978.
Structure of Cdc42 in complex with the GTPase-binding domain of the 'Wiskott-Aldrich syndrome' protein. 总被引:16,自引:0,他引:16
N Abdul-Manan B Aghazadeh G A Liu A Majumdar O Ouerfelli K A Siminovitch M K Rosen 《Nature》1999,399(6734):379-383
The Rho-family GTP-hydrolysing proteins (GTPases), Cdc42, Rac and Rho, act as molecular switches in signalling pathways that regulate cytoskeletal architecture, gene expression and progression of the cell cycle. Cdc42 and Rac transmit many signals through GTP-dependent binding to effector proteins containing a Cdc42/Rac-interactive-binding (CRIB) motif. One such effector, the Wiskott-Aldrich syndrome protein (WASP), is postulated to link activation of Cdc42 directly to the rearrangement of actin. Human mutations in WASP cause severe defects in haematopoletic cell function, leading to clinical symptoms of thrombocytopenia, immunodeficiency and eczema. Here we report the solution structure of a complex between activated Cdc42 and a minimal GTPase-binding domain (GBD) from WASP. An extended amino-terminal GBD peptide that includes the CRIB motif contacts the switch I, beta2 and alpha5 regions of Cdc42. A carboxy-terminal beta-hairpin and alpha-helix pack against switch II. The Phe-X-His-X2-His portion of the CRIB motif and the alpha-helix appear to mediate sensitivity to the nucleotide switch through contacts to residues 36-40 of Cdc42. Discrimination between the Rho-family members is likely to be governed by GBD contacts to the switch I and alpha5 regions of the GTPases. Structural and biochemical data suggest that GBD-sequence divergence outside the CRIB motif may reflect additional regulatory interactions with functional domains that are specific to individual effectors. 相似文献
979.
980.
Metamorphic core complexes are domal uplifts of metamorphic and plutonic rocks bounded by shear zones that separate them from unmetamorphosed cover rocks. Interpretations of how these features form are varied and controversial, and include models involving extension on low-angle normal faults, plutonic intrusions and flexural rotation of initially high-angle normal faults. The D'Entrecasteaux islands of Papua New Guinea are actively forming metamorphic core complexes located within a continental rift that laterally evolves to sea-floor spreading. The continental rifting is recent (since approximately 6 Myr ago), seismogenic and occurring at a rapid rate ( approximately 25 mm yr-1). Here we present evidence-based on isostatic modelling, geological data and heat-flow measurements-that the D'Entrecasteaux core complexes accommodate extension through the vertical extrusion of ductile lower-crust material, driven by a crustal density inversion. Although buoyant extrusion is accentuated in this region by the geological structure present-which consists of dense ophiolite overlaying less-dense continental crust-this mechanism may be generally applicable to regions where thermal expansion lowers crustal density with depth. 相似文献