Mitotic inhibition of clathrin-mediated endocytosis

Endocytosis and mitosis are fundamental processes in a cell’s life. Nearly 50 years of research suggest that these processes are linked and that endocytosis is shut down as cells undergo the early stages of mitosis. Precisely how this occurs at the molecular level is an open question. In this review, we summarize the early work characterizing the inhibition of clathrin-mediated endocytosis and discuss recent challenges to this established concept. We also set out four proposed mechanisms for the inhibition: mitotic phosphorylation of endocytic proteins, altered membrane tension, moonlighting of endocytic proteins, and a mitotic spindle-dependent mechanism. Finally, we speculate on the functional consequences of endocytic shutdown during mitosis and where an understanding of the mechanism of inhibition will lead us in the future.     

Pixel switching of epitaxial Pd/YHx/CaF2 switchable mirrors

Exposure of rare-earth films to hydrogen can induce a metal-insulator transition, accompanied by pronounced optical changes. This 'switchable mirror' effect has received considerable attention from theoretical, experimental and technological points of view. Most systems use polycrystalline films, but the synthesis of yttrium-based epitaxial switchable mirrors has also been reported. The latter form an extended self-organized ridge network during initial hydrogen loading, which results in the creation of micrometre-sized triangular domains. Here we observe homogeneous and essentially independent optical switching of individual domains in epitaxial switchable mirrors during hydrogen absorption. The optical switching is accompanied by topographical changes as the domains sequentially expand and contract; the ridges block lateral hydrogen diffusion and serve as a microscopic lubricant for the domain oscillations. We observe the correlated changes in topology and optical properties using in situ atomic force and optical microscopy. Single-domain phase switching is not observed in polycrystalline films, which are optically homogeneous. The ability to generate a tunable, dense pattern of switchable pixels is of technological relevance for solid-state displays based on switchable mirrors.     

Sexual conflict reduces offspring fitness in zebra finches

Parental care is often costly; hence, in sexually reproducing species where both male and female parents rear their offspring (biparental care), sexual conflict over parental investment can arise. Such conflict occurs because each care-giver would benefit from withholding parental investment for use with another partner, leading to a reduction in the amount of care given by one parent at the expense of the other. Here we report experiments to explore the prediction from theory that parents rearing offspring alone may provide greater parental investment than when rearing offspring together with a partner. We found that when the number of offspring per parent, and hence the potential workload, were kept constant, offspring received a greater per capita parental investment from single females than from both parents working together, and that males reared by single mothers were more sexually attractive as adults than their biparentally reared siblings. This difference between single- and two-parent families is due to a reduction in care provided by females when they care together with a male, rather than laziness by males or differences in the begging behaviour of chicks, supporting the claim that sexual conflict in biparental care can reduce the quality of offspring raised.     

大叶白麻叶化学成分的研究

从大叶白麻[poacynumhendersonii(Hookf)woodson]叶中分得2个木脂素类化舍物,经理化常数测定和光谱分析,分别鉴定为(-)-丁香脂素[(-)-Syringaresino1]和( )-松脂素-4-O-β-D-葡萄糖甙[( )-Pinoresionol-4-0-β-D-glucopyranoside].     

Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA

Tandem-repetitive minisatellite regions in vertebrate DNA frequently show substantial allelic variation in the number of repeat units. This variation is thought to arise through processes such as unequal crossover or replication slippage. We show here that the spontaneous mutation rate to new length alleles at extremely variable human minisatellites is sufficiently high to be directly measurable in human pedigrees. The mutation rate at different loci increases with variability in accord with the neutral mutation/random drift hypothesis, and rises to 5% per gamete for the most unstable human minisatellite isolated. Mutations are sporadic, occur with similar frequencies in sperm and oocytes, and can involve the gain or loss of substantial numbers of repeat units, consistent with length changes arising primarily by unequal exchange at meiosis. Germline instability must therefore be taken into account when using hypervariable loci as genetic markers, particularly in pedigree analysis and parenthood testing.     

The cellular functions of clathrin

Membranes and proteins are moved around the cell in small vesicles. A protein coat aids the budding of such vesicles from donor membranes. The major type of coat used by the cell is composed of clathrin, a three-legged protein that can form lattice-like coats on membranes destined for trafficking. In this review, I outline what we know about clathrin and discuss some recent advances in understanding the basic biology of this fascinating molecule, which include building a molecular model of a clathrin lattice and discovery of a new function for clathrin that occurs during mitosis. Received 12 December 2005; received after revision 21 March 2006; accepted 29 March 2006     

Clathrin is required for the function of the mitotic spindle

Clathrin has an established function in the generation of vesicles that transfer membrane and proteins around the cell. The formation of clathrin-coated vesicles occurs continuously in non-dividing cells, but is shut down during mitosis, when clathrin concentrates at the spindle apparatus. Here, we show that clathrin stabilizes fibres of the mitotic spindle to aid congression of chromosomes. Clathrin bound to the spindle directly by the amino-terminal domain of clathrin heavy chain. Depletion of clathrin heavy chain using RNA interference prolonged mitosis; kinetochore fibres were destabilized, leading to defective congression of chromosomes to the metaphase plate and persistent activation of the spindle checkpoint. Normal mitosis was rescued by clathrin triskelia but not the N-terminal domain of clathrin heavy chain, indicating that stabilization of kinetochore fibres was dependent on the unique structure of clathrin. The importance of clathrin for normal mitosis may be relevant to understanding human cancers that involve gene fusions of clathrin heavy chain.     

Deletion of genes on chromosome 1 in endocrine neoplasia

Recent studies have identified normal cellular DNA sequences which are lost in the development of embryonal and adult tumours. These tumours are thought to arise after a primary mutation in one allele of such a sequence is followed by loss of its normal homologue. In familial cases, the primary mutation is transmitted in the germ line. The secondary mutation may involve a substantial loss of chromosomal material and thus lead to identification of the site of the inherited mutation. We have examined constitutional and tumour genotypes of medullary thyroid carcinomas and phaeochromocytomas which develop in the dominantly inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2) to locate the predisposing gene in this syndrome. We observed deletion of a hypervariable region of DNA on the short arm of chromosome 1 in seven out of fourteen tumours. Analysis of the parental origin of the deleted allele in two families showed that it was derived from the affected parent in one case, which suggests that the deletion does not reflect the site of the inherited mutation in MEN2. The deleted region is distal to the breakpoint commonly detected in neuroblastomas, which share with the tumours of MEN2 embryological origin from neuroectoderm.