Involvement of small Ras GTPases and their effectors in chronic renal disease

The mechanisms involved in the development of renal fibrosis are poorly understood. Small Ras GTPases control cell proliferation, differentiation, cellular growth and apoptosis, with cell-specific expression in the kidney. Cytokines, high glucose medium or advanced glycation end-products activate Ras in different renal cells. Increased Ras activation has been found in experimental tubulointerstitial fibrosis. Transforming growth factor-β1 (TGF-β1) and Ras signalling pathways are close related: TGF-β1 overcomes Ras mitogenic effects, and Ras counteracts TGF-β signalling. However, Ras activation is also an intracellular signal transduction point for several molecules (e.g. TGF-β1) involved in kidney damage. Ras isoforms play different roles in regulating extracellular matrix synthesis in fibroblasts and mesangial cells. These data give evidence for a role for Ras in renal fibrosis, but no reviews are available on the role of p21 Ras in this process. Thus, our goal is to review the role of Ras activation and signalling in renal fibrosis. Received 7 June 2007; received after revision 17 September 2007; accepted 1 October 2007     

The Ras family of GTPases in cancer cell invasion

The ability of tumoral cells to invade surrounding tissues is a prerequisite for metastasis. This is the most life-threatening event of tumor progression, and so research is intensely focused on elucidating the mechanisms responsible for invasion and metastasis. The Ras superfamily of GTPases comprises several subfamilies of small GTP-binding proteins whose functions include the control of proliferation, differentiation, and apoptosis, as well as cytoskeleton organization. The development of metastasis is a multistep process that requires coordinated activation of proliferation, motility, changes in normal cell-to-cell and cell-to-substrate contacts, degradation of extracellular matrix, inhibition of apoptosis, and adaptation to an inappropriate tissue environment. Several members of the Ras superfamily of proteins have been implicated in these processes. The present review summarizes the current knowledge in this field.     

A small GTPase, human Rab32, is required for the formation of autophagic vacuoles under basal conditions

Here we show that a small GTPase, Rab32, is a novel protein required for the formation of autophagic vacuoles. We found that the wild-type or GTP-bound form of human Rab32 expressed in HeLa and COS cells is predominantly localized to the endoplasmic reticulum (ER), and overexpression induces the formation of autophagic vacuoles containing an autophagosome marker protein LC3, the ER-resident protein calnexin and endosomal/lysosomal membrane protein LAMP-2, even under nutrient-rich conditions. The recruitment of Rab32 to the ER membrane was necessary for autophagic vacuole formation, suggesting involvement of the ER as a source of autophagosome membranes. In contrast, the expression of the inactive form of, or siRNA-specific for, Rab32 caused the formation of p62/SQSTM1 and ubiquitinated protein-accumulating aggresome-like structures and significantly prevented constitutive autophagy. We postulate that Rab32 facilitates the formation of autophagic vacuoles whose membranes are derived from the ER and regulates the clearance of aggregated proteins by autophagy. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Production of common enterobacterial antigen by members of the family enterobacteriaceae

Zusammenfassung Nachweis eines allen Enterobakterien gemeinsamen Antigens. Sämtliche Stämme, bestehend aus 5 Familien und 12 Genera, erzeugten das Antigen, welches durch passive Haemagglutination, passive Haemolyse und Haemagglutinations-Hemmungsreaktion nachgewiesen werden konnte.     

Circular proteoglycans from sponges: first members of the spongican family

Species-specific cell adhesion in marine sponges is mediated by a new family of modular proteoglycans whose general supramolecular structure resembles that of hyalectans. However, neither their protein nor their glycan moieties have significant sequence homology to other proteoglycans, despite having protein subunits equivalent to link proteins and to proteoglycan monomer core proteins, and glycan subunits equivalent to hyaluronan and to the glycosaminoglycans of hyalectans. In some species, these molecular components are assembled into a structure with a circular core formed by the link protein- and hyaluronan-like subunits. Besides their involvement in cell adhesion, these sponge proteoglycans, for which we propose the term spongicans, participate in signal transduction processes and are suspected to play a role in sponge self-nonself recognition. Their in vivo roles and the mild methods used to purify large amounts of functionally active spongicans make them ideal models to study the functions and possible new applications of proteoglycans in biomedical research. Received 21 May 2002; received after revision 5 July 2002; accepted 10 July 2002 RID="*" ID="*"Corresponding author.     

Structure and function of interleukin-22 and other members of the interleukin-10 family

The IL-10 family of cytokines is comprised of IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and IFN-λs (IL-28A, IL-28B, and IL-29). The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved in several human diseases and health conditions and hence their structural analyses may provide valuable information to design specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin physiology and physiopathology.     

Insulin resistance and related electrical activity of the small intestine

Summary Postprandial disruption of the migrating myoelectric complex is of longer duration in obese hyperinsulemic Zucker rats than in control rats. No postprandial disruption was seen in an insulin resistant dog. This gives further support to a major role for insulin in control of gut activity.     

All in the family: aldose reductase and closely related aldo-keto reductases

Aldose reductase catalyzes the first step in the polyol pathway and is thought to be involved in the pathogenesis of diabetic complications. In addition to polyol synthesis, aldose reductase may have multiple other activities that intersect with signal processing and oxidative defense mechanisms. Multiple aldose reductase-like proteins have been discovered to have structures and catalytic properties that broadly overlap those of aldose reductase. This chapter will summarize new insights into properties and functions of aldose reductase and closely related members of the aldo-keto reductase enzyme superfamily.     

The formation of disulfide bonds in human protamines during sperm maturation

Summary The disulfide contents of human sperm heads, as measured by reduction to the sulfhydryls and subsequent alkylation with¹⁴C-iodoacetamide, increase about 2-fold during the sperm passage from the caput to caudal epididymides. Majority of the increased disulfides reside in the human protamine fractions.We thank Drs Jisnuson Svasti and Nongnuj Tanphaichitr for their valuable suggestions. This work was supported by the Faculty of Science, Mahidol University, and the Rockefeller Foundation.     

The formation of disulfide bonds in human protamines during sperm maturation.

The disulfide contents of human sperm heads, as measured by reduction to the sulfhydryls and subsequent alkylation with 14C-iodoacetamide, increase about 2-fold during the sperm passage from the caput to caudal epididymides. Majority of the increased disulfides resides in the human protamine fractions.     

Small Rho GTPases in the control of cell shape and mobility

Rho GTPases are a class of evolutionarily conserved proteins comprising 20 members, which are predominantly known for their role in regulating the actin cytoskeleton. They are primarily regulated by binding of GTP/GDP, which is again controlled by regulators like GEFs, GAPs, and RhoGDIs. Rho GTPases are thus far well known for their role in the regulation of actin cytoskeleton and migration. Here we present an overview on the role of Rho GTPases in regulating cell shape and plasticity of cell migration. Finally, we discuss the emerging roles of ubiquitination and sumoylation in regulating Rho GTPases and cell migration.     

Effect of epidermal growth factor on growth and maturation of fetal and neonatal rat small intestine in organ culture

Small intestinal explants from pre- and post-natal rats were incubated in an organ culture system in the absence and presence of epidermal growth factor (EGF). The rate of synthesis of small intestinal DNA and protein as well as the activity of lactase and alkaline phosphatase increased rapidly between 17 and 20-day gestational age, whereafter they declined. The maximal incorporation of 3H-thymidine and 14C-alanine into DNA and protein, respectively, was significantly stimulated by EGF (100 ng/ml). EGF had no effect on the activity of either lactase or alkaline phosphatase in the small intestinal explants.     

Effect of epidermal growth factor on growth and maturation of fetal and neonatal rat small intestine in organ culture

Summary Small intestinal explants from pre- and post-natal rats were incubated in an organ culture system in the absence and presence of epidermal growth factor (EGF). The rate of synthesis of small intestinal DNA and protein as well as the activity of lactase and alkaline phosphatase increased rapidly between 17 and 20-day gestational age, whereafter they declined. The maximal incorporation of³H-thymidine and¹⁴C-alanine into DNA and protein, respectively, was significantly stimulated by EGF (100 ng/ml). EGF had no effect on the activity of either lactase or alkaline phosphatase in the small intestinal explants.Acknowledgment. The project was supported by grants from the Veterans Administration Research Service. The authors wish to thank Dr. M. C. Geokas, Chief, Department of Medicine, Veterans Administration Medical Center, Martinez, CA, for providing us with excellent laboratory facilities and for his encouragement in this study.     

Rab protein evolution and the history of the eukaryotic endomembrane system

Spectacular increases in the quantity of sequence data genome have facilitated major advances in eukaryotic comparative genomics. By exploiting homology with classical model organisms, this makes possible predictions of pathways and cellular functions currently impossible to address in intractable organisms. Echoing realization that core metabolic processes were established very early following evolution of life on earth, it is now emerging that many eukaryotic cellular features, including the endomembrane system, are ancient and organized around near-universal principles. Rab proteins are key mediators of vesicle transport and specificity, and via the presence of multiple paralogues, alterations in interaction specificity and modification of pathways, contribute greatly to the evolution of complexity of membrane transport. Understanding system-level contributions of Rab proteins to evolutionary history provides insight into the multiple processes sculpting cellular transport pathways and the exciting challenges that we face in delving further into the origins of membrane trafficking specificity.     

Oocyte maturation in vitro: Contribution of the oviduct to total maturation inXenopus laevis

Summary Contact of progesterone matured oocytes ofXenopus laevis with the oviduct reduces the time necessary to attain cleavage capacity from 24 h to 3 h. Full maturity has been demonstrated by normal development of the matured eggs after fertilization.     

Oocyte maturation in vitro: contribution of the oviduct to total maturation in Xenopus laevis.

Contact of progesterone matured oocytes of Xenopus laevis with the oviduct reduces the time necessary to attain cleavage capacity from 24 h to 3 h. Full maturity has been demonstrated by normal development of the matured eggs after fertilization.