Constitutive Activation of the Calcium Sensor STIM1 Causes Tubular-Aggregate Myopathy

Tubular aggregates are regular arrays of membrane tubules accumulating in muscle with age. They are found as secondary features in several muscle disorders, including alcohol- and drug-induced myopathies, exercise-induced cramps, and inherited myasthenia, but also exist as a pure genetic form characterized by slowly progressive muscle weakness. We identified dominant STIM1 mutations as a genetic cause of tubular-aggregate myopathy (TAM). Stromal interaction molecule 1 (STIM1) is the main Ca²⁺ sensor in the endoplasmic reticulum, and all mutations were found in the highly conserved intraluminal Ca²⁺-binding EF hands. Ca²⁺ stores are refilled through a process called store-operated Ca²⁺ entry (SOCE). Upon Ca²⁺-store depletion, wild-type STIM1 oligomerizes and thereby triggers extracellular Ca²⁺ entry. In contrast, the missense mutations found in our four TAM-affected families induced constitutive STIM1 clustering, indicating that Ca²⁺ sensing was impaired. By monitoring the calcium response of TAM myoblasts to SOCE, we found a significantly higher basal Ca²⁺ level in TAM cells and a dysregulation of intracellular Ca²⁺ homeostasis. Because recessive STIM1 loss-of-function mutations were associated with immunodeficiency, we conclude that the tissue-specific impact of STIM1 loss or constitutive activation is different and that a tight regulation of STIM1-dependent SOCE is fundamental for normal skeletal-muscle structure and function.     

C1D family proteins in coordinating RNA processing,chromosome condensation and DNA damage response

Research on the involvement of C1D and its yeast homologues Rrp47 (S. cerevisiae) and Cti1 (S. pombe) in DNA damage repair and RNA processing has remained mutually exclusive, with most studies predominantly concentrating on Rrp47. This review will look to reconcile the functions of these proteins in their involvement with the RNA exosome, in the regulation of chromatin architecture, and in the repair of DNA double-strand breaks, focusing on non-homologous end joining and homologous recombination. We propose that C1D is situated in a central position to maintain genomic stability at highly transcribed gene loci by coordinating these processes through the timely recruitment of relevant regulatory factors. In the event that the damage is beyond repair, C1D induces apoptosis in a p53-dependent manner.     

Effect of light environment on intra-specific variation in herbivory in the carnivorous plant Pinguicula moranensis (Lentibulariaceae)

Identifying the factors that affect a plant’s probability of being found and damaged by herbivores has been a central topic in the study of herbivory. Although herbivory could have important negative consequences on carnivorous plants, their interaction with herbivores remains largely unexplored. We evaluated the effect of spatial variation in light environment (sunny, shade and full-shade sites) on the pattern of leaf herbivory and florivory of the carnivorous plant Pinguicula moranensis. Plants’ overall probability of leaf damage was high (74.24%). Mean herbivory was four times higher in the sunny and shade sites than the observed in the full-shade site. Nearly 8% of plants suffered damage to reproductive structures, although the probability of florivory was similar among sites. Discussion addressed the inter-site variation in mean herbivory considering the effect of light exposure and the impact that herbivory could have on fitness components of this carnivorous plant.     

Simultaneous Regulation of Cytokinetic Furrow and Nucleus Positions by Cortical Tension Contributes to Proper DNA Segregation during Late Mitosis

1. Download : Download high-res image (211KB)
2. Download : Download full-size image

     

Fluorescent in situ hybridization of the telomere repeat sequence in hamster sperm nuclear structures

The flat, hooked-shaped architecture of the hamster sperm nucleus makes this an excellent model for in situ hybridization studies of the three dimensional structure of the genome. We have examined the structure of the telomere repeat sequence (TTAGGG)_n with respect to the various nuclear structures present in hamster spermatozoa, using fluorescent in situ hybridization. In fully condensed, mature sperm nuclei, the telomere sequences appeared as discrete spots of various sizes interspersed throughout the volume of the nuclei. While the pattern of these signals was non-random, it varied significantly in different nuclei. These discrete telomere foci were seen to gradually lengthen into linear, beaded signals as sperm nuclei were decondensed, in vitro, and were not associated with the nuclear annulus. We also examined the relationship of telomeres to the sperm nuclear matrix, a residual nuclear structure that retains the original size and shape of the nucleus. In these structures the DNA extends beyond the perimeter of the nucleus to form a halo around it, representing the arrangement of the chromosomal DNA into loop domains attached at their bases to the nuclear matrix. Telomere signals in these structures were also linear and equal in length to those of the decondensed nuclei, and each signal represented part of a single DNA loop domain. The telomeres were attached at one end to the nuclear matrix and extended into the halo. Sperm nuclear matrices treated with Eco RI retained the telomere signals. These data support sperm DNA packaging models in which DNA is coiled into discrete foci, rather than spread out linearly along the length of the sperm nucleus.