Ropporin has been identified as a spermatogenic cell-specific protein and may be involved in sperm maturation, motility, capacitation, hyperactivation and acrosome reaction. However, latest studies have shown that Ropporin is expressed weakly in normal non-testis tissues and highly in hematologic malignancies. Its highly conservative expression in mammalians demonstrates its importance to life. This paper updates the characterization, expression and its distribution, and biological function of Ropporin, and the advances in the clinical researches of the protein.
Animals ; Humans ; Male ; Membrane Proteins ; physiology ; Spermatogenesis ; rho GTP-Binding Proteins ; physiology

G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas β-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of β-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of β-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or β-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or β-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.
Bias (Epidemiology)* ; Felodipine ; GTP-Binding Proteins ; Humans ; Ligands ; Pathology* ; Physiology* ; Transducers

During mitosis, the allocation of genetic material concurs with organelle transformation and distribution. The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression, cell fate determination, and organismal homeostasis. Small GTPases belonging to the Ras superfamily regulate various cell organelles during division. Being the key regulators of membrane dynamics, the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases, such as cancer and Alzheimer's disease. Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation. This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.
Humans ; Mitosis ; Monomeric GTP-Binding Proteins ; Neoplasms ; Organelles/physiology* ; Signal Transduction

BACKGROUNDMelanoma has the highest mortality among all superficial malignant tumors. The poor prognosis is due to its high metastasis rate and the lack of therapeutic targets. As a molecular switch that controls tumor metastasis, Ras homology C (RhoC) has been correlated with tumor progression, especially tumor invasion and metastasis. However, little research has been done about the effects of RNA interference (RNAi) targeting RhoC on the invasion and metastasis of melanoma. In this study, we constructed an RNAi lentivirus vector targeting the RhoC gene of melanoma cells and identified its silencing effects on the RhoC gene.

METHODSBased on the RhoC gene encoding information, three pGPU6/GFP/Neo-short hairpin (shRNA) plasmids were constructed. After detecting their silencing effects on the RhoC gene of A375 cells, the most effective pGPU6/GFP/Neo-shRNA plasmid was packed with lentivirus to construct the recombinant pLenti6.3-EGFP-453 targeting RhoC. The lentivirus vector was used to infect A375 cells, and then the expression of RhoC mRNA and protein were determined with real-time PCR and Western blotting.

RESULTSThe plasmids pGPU6/GFP/Neo-shRNA 336, pGPU6/GFP/Neo-shRNA 453, and pGPU6/GFP/Neo-shRNA 680 were constructed. After they were transfected into A375 cells, the expressions of RhoC mRNA and protein were 1.47 ± 0.26, 1.13 ± 0.16, 1.39 ± 0.11 and 70.98 ± 9.21, 50.67 ± 6.06, 65.77 ± 4.06, respectively. pGPU6/GFP/Neo-shRNA 453 was the most effective sequence, and was used to successfully construct the pLenti6.3-EGFP-453 lentiviral vector targeting RhoC. pLenti6.3-EGFP-453 was used to infect A375 cells. The expression of RhoC mRNA and protein were 1.05 ± 0.05 and 62.04 ± 15.86 in the lentivirus group, 4.21 ± 0.24 and 220.86 ± 24.07 in the negative lentivirus control group, and 4.63 ± 0.32 and 257.39 ± 12.30 in the normal control group respectively with the difference between the lentivirus group and the control groups being statistically significant (P < 0.05).

CONCLUSIONThe successfully constructed pLenti6.3-EGFP-453 vector targeting the RhoC can effectively infect human melanoma A375 cells in vitro, and significantly inhibit the RhoC mRNA and protein expression.

Cell Line, Tumor ; Genetic Vectors ; genetics ; Humans ; Lentivirus ; genetics ; Melanoma ; genetics ; therapy ; RNA Interference ; physiology ; rho GTP-Binding Proteins ; genetics ; metabolism ; rhoC GTP-Binding Protein

Active Transport, Cell Nucleus ; physiology ; Animals ; Cell Nucleus ; physiology ; Cilia ; physiology ; Humans ; Molecular Motor Proteins ; physiology ; beta Karyopherins ; physiology ; ran GTP-Binding Protein ; physiology

It is far from understood why we forget things that are known to us seconds ago. Emerging evidence emphasizes that small G protein Rac could be a key to understanding this type of rapid early memory forgetting. This current perspective article will first review these studies and then discuss their implications for the internal processes underlying forgetting.
Animals ; Drosophila Proteins ; physiology ; Drosophila melanogaster ; physiology ; Humans ; Memory ; physiology ; Oxidation-Reduction ; Retention (Psychology) ; Signal Transduction ; rac GTP-Binding Proteins ; physiology

The researches on Rho family proteins have been progressing very fast recently. Rho proteins mainly regulate the reorganization of actin cytoskeleton, thus controlling the cell morphologic changes and the motility. There is a close relationship between Rho proteins and tumors; under the function of regulators and effectors, the activation of Rho proteins can enhance cell motility, induce gene expression in cell cycle progression, and promote the degradation and re-establishment of extracellular matrix. Accordingly, Rho proteins play a crucial role in regulating tumor cells' proliferation, apoptosis, invasion, metastasis and other biological behaviors. Further researches on Rho proteins can help to clarify the mechanism involved in these effects, thus providing a potential evidence in anti-tumor therapy.
Actins ; metabolism ; Apoptosis ; physiology ; Cell Movement ; physiology ; Cell Proliferation ; Cytoskeleton ; metabolism ; physiology ; Humans ; Neoplasms ; metabolism ; pathology ; rho GTP-Binding Proteins ; metabolism ; physiology

Neutrophils play a major role in host defense against microbial infection. There are some clues indicate that neutrophils may also play a role in the pathophysiology of the airway obstruction in chronic asthma. We studied the roles of intracellular calcium and GTP gamma S in the regulation of neutrophils exocytosis using pipette perfusion and membrane capacitance measurement technique in whole cell patch clamp configuration. The results showed that the membrane capacitance increase induced by calcium revealed a biphasic process. The first phase occurred when the calcium level was between 0.2-14 micromol/L with a plateau amplitude of 1.23 pF and a calcium EC50 of 1.1 micromol/L. This phase might correspond to the release of the tertiary granules. The second phase occurred when the calcium concentration was between 20-70 micromol/L with a plateau increment of 6.36 pF, the calcium EC50 being about 33 micromol/L. This phase might represent the release of the primary and secondary granules. Intracellular calcium also simultaneously increased the exocytotic rate and the eventual extent in neutrophils. On the other hand, GTP gamma S can increase the exocytotic rate in a dose-dependent manner but had no effect on the eventual extent of membrane capacitance increment (>6 pF) if the cell was stimulated for a long period (>20 min). GTP gamma S (ranging from 20 to 100 micromol/L) induced the neutrophils to release all four types of the granules at very low intracellular calcium level.
Calcium ; metabolism ; Cell Degranulation ; drug effects ; Exocytosis ; drug effects ; GTP-Binding Proteins ; metabolism ; physiology ; Guanosine Triphosphate ; analogs & derivatives ; pharmacology ; Humans ; Neutrophils ; metabolism ; physiology ; Patch-Clamp Techniques

OBJECTIVETo explore the protein factors that could interact with the testis-specific protein encoded by HSD-3.8 gene (GenBank Accession Number AF311312) related with female fertilization.

METHODSYeast two-hybrid system was used to screen the human ovary MATCHMAKER cDNA library with constructed "bait plasmid" containing the 0.7 kb fragment (HSD-0.7) of HSD-3.8. The interaction with the positive fragments using a series of truncated bait plasmids was investigated.

RESULTSOne positive gene fragment was obtained, which coded for 144 amino acids of the C-terminus of human G protein beta subunit 1. Truncated bait plasmids couldn't interact with the fish protein fragment in yeast.

CONCLUSIONSThe protein encoded by HSD-3.8 gene may function through G protein signal transduction pathway and the interaction depends on the integration of the bait protein.

Adenosine Triphosphate ; metabolism ; Adult ; Antigens, Surface ; DNA-Binding Proteins ; genetics ; Female ; GTP-Binding Proteins ; genetics ; physiology ; Gene Library ; Humans ; Male ; Protein Biosynthesis ; Proteins ; genetics ; Spermatozoa ; chemistry ; physiology ; Synaptophysin ; Testis ; chemistry ; Two-Hybrid System Techniques ; Yeasts ; genetics

The SAM and HD domain containing protein 1 (Sterile alpha motif domain and HD domain-containing protein 1, SAMHD1) is a putative negative regulator of the antiviral innate immune response. It can significantly increase the antiviral immune response, mediates the interferon-induced inflammatory response involved in the host foreign-virus defense system. The early studies have focused on its gene mutations associated with Aicardi-Goutières syndrome (AGS), the latest study found that SAMHD1 as a potent dGTP-stimulated triphosphohydrolase restricts HIV-1 replication by hydrolyzing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral complementary DNA (cDNA) synthesis. Auxiliary gene of HIV-2 and simian immunodeficiency virus (SIVsm / mac) encoding the Vpx protein can eliminate HIV-1 restriction. In recent years, the research on SAMHD1, mores forward rapidly this paper overviews the recent research progression related to the above fields.
Animals ; Cell Line ; HIV ; metabolism ; physiology ; Humans ; Monomeric GTP-Binding Proteins ; genetics ; metabolism ; SAM Domain and HD Domain-Containing Protein 1 ; Viral Regulatory and Accessory Proteins ; metabolism