Insulin-stimulated glucose uptake in adipocytes is mediated by translocation of vesicles containing the glucose transporter GLUT4 from intracellular storage sites to the cell periphery and the subsequent fusion of these vesicles with the plasma membrane, resulting in the externalization of GLUT4. Fusion of the GLUT4-containing vesicles with the plasma membrane is mediated by a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex consisting of vesicle-associated membrane protein 2 (VAMP2), 23-kDa synaptosomal-associated protein (SNAP23), and syntaxin4. We have now generated mouse embryos deficient in the syntaxin4 binding protein Munc18c and show that the insulininduced appearance of GLUT4 at the cell surface is enhanced in adipocytes derived from these Munc18c −/−

Although chromosomal segregation at meiosis I is the critical process for genetic reassortment and inheritance, little is known about molecules involved in this process in metazoa. Here we show by utilizing doublestranded RNA (dsRNA)-mediated genetic interference that novel protein kinases (Ce-CDS-1 and Ce-CDS-2) related to Cds1 (Chk2) play an essential role in meiotic recombination in Caenorhabditis elegans. Injection of dsRNA into adult animals resulted in the inhibition of meiotic crossing over and induced the loss of chiasmata at diakinesis in oocytes of F 1 animals. However, electron microscopic analysis revealed that synaptonemal complex formation in pachytene nuclei of the same progeny of injected animals appeared to be normal. Thus, Ce-CDS-1 and Ce-CDS-2 are the first example of Cds1-related kinases that are required for meiotic recombination in multicellular organisms.Protein kinases play crucial roles in the regulation of a wide variety of cellular functions. A novel family of protein kinases, bearing a phosphospecific protein-protein interaction motif, the forkhead-associated (FHA) domain (11), has been identified and shown to be involved in checkpoint regulation and DNA repair induced by DNA damage (16). Protein kinases belonging to this family include Saccharomyces cerevisiae Rad53, Dun1, and Mek1p (MRE4), Schizosaccharomyces pombe Cds1 and Mek1, Drosophila melanogaster Dmnk, and mammalian Chk2 (5,7,19,20,23,26,36,43). It has been reported that the yeast Rad53, Cds1, and Dun1 protein kinases are required for the S-phase checkpoint and for the activation of the DNA repair machinery upon DNA damage, although Dun1 is involved only in the latter process (2,12,23,25,36,42,43). In contrast, S. cerevisiae Mek1p is involved in the regulation of meiotic recombination (19).It has recently been reported that, in response to DNA damage and DNA replicational stress, Chk2 (mammalian Cds1) is activated and phosphorylates Cdc25C, thereby inactivating Cdc25 phosphatase activity and preventing entry of cells into mitosis (5,7,8,20,39). More recently, Chk2 has been shown to stabilize p53 by phosphorylating p53 on serine 20, which interferes with Mdm2 binding (9,14,35). In contrast, D. melanogaster Dmnk, which is most closely related to Chk2, is highly expressed in ovaries and in germ cell nuclei during early embryogenesis, suggesting its possible function(s) in char- acteristic features of germ cells such as meiosis and/or germline establishment (26).Caenorhabditis elegans is an excellent model organism in which to study meiosis, the cell cycle, and development. With the determination of the entire genomic sequence of C. elegans, this multicellular organism further provides a unique opportunity to study the role of this entire gene family during development. Specific and functional disruption of gene expression by utilizing double-stranded RNA (dsRNA)-mediated genetic interference (RNAi) enables us to address the biological consequence of reduction or elimination of the activity of a particular gene (4,13,34). To exam...

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The early development of the lens was examined, using 36 externally normal human embryos at Carnegie stages 13–23 (4 to 8 weeks of gestation). Twenty-two embryos were sectioned serially and stained with periodic acid-Schiff and a modified method of PAS. In 14 embryos, not only the differential distribution of glycogen but also the ultrastructural change in the developing lens, with special reference to junctional complexes, were examined electron microscopically. At stage 15, when the lens vesicle was formed, glycogen was observed in the cytoplasm of the lens epithelium, especially in the posterior lens epithelium. From stages 16 to 18, when the posterior lens epithelium was differentiated into the primary lens fibers and elongated toward the anterior lens epithelium, the amount of glycogen increased in the basal cytoplasm of the primary lens fiber, where the intracellular organelles, such as the tubular vesicles, mitochondria and multivesicular bodies, began to aggregate. At stage 20, when the lens cavity was obliterated, glycogen was also present in the anterior lens epithelium. At stage 21, as the formation of the secondary lens fibers proceeded, glycogen was noted in the secondary lens fibers in the equator region. These findings suggest that the distribution of glycogen is associated with the formation of the primary and secondary lens fibers. In addition, we provide additional information that a lot of glycogen is distributed in the region where many intracellular organelles aggregate in the embryonic lens vesicles.