We investigated unknown in vivo functions of Torsin by using Drosophila as a model. Downregulation of Drosophila Torsin (DTor) by DTor specific inhibitory double-stranded RNA (RNAi) induced abnormal locomotor behavior and increased susceptibility to H2O2. In addition, altered expression of DTor significantly increased the numbers of synaptic boutons. One of important biochemical consequence of DTor-RNAi expression in fly brains was up-regulation of alcohol dehydrogenase (ADH). Altered expression of ADH has also been reported in Drosophila Fragile-X mental retardation protein (DFMRP) mutant flies. Interestingly, expression of DFMRP was altered in DTor mutant flies, and DTor and DFMRP were present in the same protein complexes. In addition, DTor and DFMRP immunoreactivities were partially colocalized in several cellular organelles in larval muscles. Furthermore, there were no significant differences between synaptic morphologies of dfmrp null mutants and dfmrp mutants expressing DTor-RNAi. Taken together, our evidences suggested that DTor and DFMRP might be present in the same signaling pathway regulating synaptic plasticity. (This work was supported bythe basic science research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2015R1D1A3A01018497)

Inflammation mainly mediated by innate immune cells as the first line of host defense against pathogens is an acute response that limits tissue damage and eliminates pathogens in the body. In triggering inflammation, several pattern recognition receptors work together; membrane-associated Toll-like receptors, c-type lectin receptors, retinoic acid-inducible gene-like helicase receptors, absent in melanoma-like receptors, and cytosolic nucleotide-binding domain and leucine-rich repeat receptors. Among them, inflammasome is a newly trigger of inflammation in response to exogenous and endogenous stimuli and its activation leads to the assembly of multiprotein platforms composed of NLRP3 (NOD-like receptor family, pyrin domain containing 3), ASC (apoptosis associated speck-like protein containing a CARD), and procaspase 1. Thus, the activated inflammasome activates caspase 1, resulting in processing and secretion of interleukin (IL)-1β. Recent emerging data suggest that dysregulated metabolites, i.e., amyloids, ceramides, and cholesterol crystals, have been classified as inflammasome activators. In addition, IL-1β may play a critical role in the pathogenesis of chronic inflammation-induced disorders such as Alzheimer’s diseases, type 2 diabetes, and atheriosclerosis. This review introduces the basic concept of inflammasome activation and auto-inflammatory diseases. In addition, it discusses the updated signaling models of inflammasome activation that link metabolic dysfunction in order to outline future therapeutic approaches to inflammasome-mediating diseases.

To identify genes that play critical roles during male gametogenesis in Arabidopsis, we have isolated several pollen morphological mutants from a mutagenized seed pool generated with a T-DNA activation vector. In this study, we have focused on a mutant plant producing ~50% abnormal pollen grains including high levels of collapsed pollen at maturity. The pollen developmental analysis showed that the mutant pollen phenotype was first observed at tricellular stage. Interestingly, the mutation was only maintained as a heterozygote due to the severely reduced genetic transmission through both sexes. TAIL PCR analysis led to the identification of the responsible gene which encodes a conserved oligomeric golgi complex component-related protein (COGCC). RT-PCR analysis showed predominant expression of the gene in reproductive organs including developing spores. The gene identity was confirmed by the result that mutant plants harboring a T-DNA containing corresponding wild type gene produced less level of mutant pollen grains. Furthermore, confocal laser scanning microscopy using mature pollen expressing COGCC-RFP driven under the native promoter showed small punctate signals, which are likely to be from the Golgi complex. Further experiments for co-localization of the COGCC-RFP with the Golgi markers are underway.

Mammalian spermatogenesis takes place in the seminiferousepithelium, which is composed of Sertoli cells and germ cells. The interaction between spermatogenic and Sertoli cells as well as elongated spermatids and Sertoli cells is tightly regulated by junctional adhesion molecules (JAMs). JAMs, which are cell adhesion molecules, are known to play roles in various biological processes such as fertilization, neurogenesis, cancer progression, and spermatogenesis. Members of the JAM family have a unique structure: they contain an N-terminal signal peptide domain, immunoglobulin (Ig)-like domains, transmembrane and cytoplasmic tail domains, each of which has distinct functions. The extracellular Ig-like domains interact in a homophilic or heterophilic manner, whereas cytoplasmic tail domain mediates the tight junction assembly. Although members of the JAM family are exclusively present in or restricted to the testis, their precise roles in spermatogenesis and fertilization have not yet been completely explored. The functional roles of Nectin-2, Nectin-3, JAM-C, cell adhesion molecule1 (CADM1), coxsackie and adenovirus receptor (CAR) have been evaluated by analysis of null mutant mice. Unfortunately, CAR-deficient mice had an embryonic lethal phenotype; this demonstrates the importance of CAR in development, but its physiological role in spermatogenesis is not known. The loss of CADM1, Nectin-3 and JAM-C resulted in male infertility caused by loss of adhesion between germ and Sertoli cells. A variety of JAMs participate in the interaction between germ and Sertoli cells. Recently, human VSIG1 has been characterized, which was originally known as A34, as a new member of the JAM family; VSIG1 is composed of two extracellular Ig-like domains, a transmembrane domain, and a cytoplasmic domain. However, this molecule has not been functionally characterized, so this was one of the aims of our present study. RT-PCR and immunoblot analyses were used to study VSIG1 expression, VSIG1 was specifically expressed in testicular germ cells but not in sperm. Pull-down assay with glutathione S-transferase (GST) or His-fused first Ig and second Ig domains of VSIG1 and SDS-PAGE under mild non-reducing conditions demonstrated that VSIG1 functions as an in vitro homophilic adhesion molecule. Furthermore, cells expressing a deletion of the C-terminus of VSIG1 failed to interact with ZO-1, the central structural protein of the tight junction. These findings suggest mouse VSIG1 interacts with an unknown molecule in Sertoli cells via its extracellular domain, while its cytoplasmic domain is needed for binding to ZO-1. Thus, we suggest mouse VSIG1 may play an important role in spermatogenesis rather than fertilization by forming heterophilic complex with a molecule similar to JAM family.