Common mechanisms for regulated exocytosis in the chromaffin cell and the synapse

Chromaffin granule exocytosis differs in many physiological respects from neuronal synaptic vesicle exocytosis, which has led to the assumption that the two processes occur by distinct mechanisms. While different mechanisms are certainly in operation for the biogenesis of granules and synaptic vesicles, it is now becoming clear that similar mechanisms are used by both beyond this stage. The similarities extend to various aspects of regulated exocytosis, including regulation of the number of vesicles released in response to cell stimulation. Most strikingly, it now appears that the same proteins mediate the docking and fusion of both chromaffin granules and synaptic vesicles, and that homologues of these proteins act similarly in constitutive membrane traffic throughout evolution.     

Gradient of distribution in Europe of the major CF mutation and of its associated haplotype

Summary In this collaborative European study, a total of 4871 cystic fibrosis (CF) chromosomes and 3539 normal chromosomes have been characterized for the haplotypes defined by the 2 extragenic polymorphic sequences revealed by XV2c and KM19. The association between one of these haplotypes (B haplotype) and the most frequent CF mutation, ΔF508, suggests for the latter a single origin and a subsequent diffusion according to a South East-North West gradient. The linkage disequilibrium data between CF and the B haplotype in different European populations are compatible with a relatively more recent appearance of the mutation in Northern Europe whereas in Southern Europe a longer history of the same mutation would have allowed time for recombination with other haplotypes. This model is also compatible with a selective advantage of carriers but does not account for (1) the excess of B haplotypes observed among both normal and non-ΔF508 CF chromosomes; (2) the correlation between the B haplotype and the severity of the phenotypic effect caused by CF mutations, as measured by pancreatic insufficiency and meconium ileus.     

Characterisation of microtubule-associated proteins at the synapse: absence of MAP 2

The high molecular weight microtubule-associated proteins MAP 1 and MAP 2 are major components of brain cytosol and can be readily identified using polyacrylamide gel electrophoresis on the basis of heat-stability and co-sedimentation with microtubules. An examination of synaptosomal cytosol, synaptic plasma membrane and postsynaptic density fractions showed that MAP 2 is absent from these fractions and thus from both pre- and postsynaptic sites. All of the fractions contained polypeptides that comigrated with MAP 1 and a MAP 1 like polypeptide was identified in a microtubule preparation from synaptosomal cytosol. The absence of MAP 2 from synaptosomal cytosol was confirmed by immunoblotting using an antibody directed against MAP 2. Immunocytochemistry using this antibody showed that MAP 2 was present in cell bodies and dendrites but absent from axons.     

The DNase I generated disomal series is coherent to 16N. Implications for coiling models of chromatin structure

The disomal series generated by the digestion of chromatin with DNase I has been followed to its highest orders using Klenow end-labelling and field-inversion gel electrophoresis to maximise the resolution of large DNA fragments. The series is coherent to the 16N level and as such is incompatible with the most structurally acceptable coiling models. We propose that this is evidence for the general unsuitability of coiling models and is support for the existence of simple 'back-to-back' double-stranded structures within chromatin.     

Increased Incorporation of [3H]Lysine into Synaptic Membranes of the Visual Cortex Following First Exposure of Dark-Reared Rats to Light Is Confined to Particular Polypeptides

Abstract: The incorporation of [³H]lysine into separated polypeptides of synaptic-membrane fractions prepared from the visual cortices of dark-reared rats and littermates exposed to light for 1 h was examined. Increased incorporation of [³H]lysine was found in synaptic membranes from light-exposed compared to dark-reared rats in polypeptides of four molecular weights: 100,000, 71,000, 44,000, and 38,000. The 44,000-molecular-weight peak has been suggested to be actin on the basis of its comigration with pure brain actin. These results indicate that increased incorporation of [³H]lysine into synaptic membranes of the visual cortex, following first exposure of dark-reared rats to light, is confined to particular polypeptides.