Arginine-rich peptides, including octaarginine (R8), HIV-1 Tat, and branched-chain arginine-rich belong to one of the major classes cell-permeable peptides which deliver various proteins macromolecules cells. The importance endocytic pathways has recently been demonstrated in cellular uptake these peptides. We have previously shown that macropinocytosis is for organization F-actin accompanies this process. In study, using proteoglycan-deficient CHO cells, we membrane-associated proteoglycans...

Plexins are cell surface receptors for semaphorin molecules, and their interaction governs adhesion migration in a variety of tissues. We report that the Semaphorin 4D (Sema4D) receptor Plexin-B1 directly stimulates intrinsic guanosine triphosphatase (GTPase) activity R-Ras, member Ras superfamily small GTP-binding proteins has been implicated promoting neurite outgrowth. This required with Rnd1, protein Rho family. Down-regulation R-Ras by Plexin-B1-Rnd1 complex was essential Sema4D-induced...

Fever is the widely known hallmark of disease and induced by action nervous system. It generally accepted that prostaglandin (PG) E₂ produced in response to immune signals then acts on preoptic area (POA), which triggers stimulation sympathetic system, resulting production fever. Actually, EP3 subtype PGE receptor, essential for induction fever, be localized POA neurons. However, neural pathway mediating pyrogenic transmission from system remains unknown. To identify neuronal...

The prostaglandin EP3 receptor (EP3R) subtype is believed to mediate large portions of diverse physiologic actions E2 in the nervous system. However, distribution EP3R protein has not yet been unveiled peripheral or central systems. authors raised a polyclonal antibody against an amino-terminal portion rat that recognized specifically protein. In this study, immunoblotting analysis with showed several immunoreactive bands different molecular weights brain extracts and membrane fractions...

Cell migration is essential for normal development and many pathological processes. Rho-family small GTPases play important roles in this event. In particular, Rac regulates lamellipodia formation at the leading edge during migration. The GTPase RhoG activates through its effector ELMO ELMO-binding protein Dock180, which functions as a Rac-specific guanine nucleotide exchange factor. Here we investigated role of cell RNA interference-mediated knockdown HeLa cells reduced Transwell...

EphA2, a member of the Eph receptor family, is frequently overexpressed in variety human cancers, including breast and promotes cancer cell motility invasion independently its ligand ephrin stimulation. In this study, we identify Ephexin4 as guanine nucleotide exchange factor (GEF) for RhoG that interacts with EphA2 cells, knockdown rescue experiments show acts downstream to promote ligand-independent migration toward epidermal growth through activation RhoG. The recruits effector ELMO2 Rac...

The Rho family of small GTPases has been shown to be involved in the regulation neuronal morphology, and Rac exert antagonistic actions neurite formation. In this study, we have examined cross-talk between relation nerve growth factor (NGF)-induced outgrowth PC12 cells. NGF induced a rapid activation Rac1 suppression RhoA activity. Constitutively active RhoA, RhoAV14, or constitutively Gα12-induced endogenous inhibited NGF-induced without any effect on extracellular signal-regulated kinase...

We previously reported that the activation of prostaglandin E receptor EP3 subtype caused neurite retraction via small GTPase Rho in EP3B receptor-expressing PC12 cells (Katoh, H., Negishi, M., and Ichikawa, A. (1996) <i>J. Biol. Chem.</i>271, 29780–29784). However, a potential downstream effector induces was not identified. Here we examined morphological effect p160 RhoA-binding kinase ROKα, target for RhoA recently identified, on nerve growth factor-differentiated cells. Microinjection...

In neuronal cells, activation of a certain heterotrimeric G protein-coupled receptor causes neurite retraction and cell rounding via the small GTPase Rho. However, specific proteins that mediate Rho-dependent have not yet been identified. Here we investigated effects expression constitutively active Gα subunits on morphology differentiated PC12 cells. Expression GTPase-deficient Gα₁₂, Gα₁₃, Gα_q, but Gα_i2, caused in These morphological changes...

The Rho family of small GTPases has been implicated in cytoskeletal reorganization and subsequent morphological changes various cell types. Among them, Rac Cdc42 have shown to be involved neurite outgrowth neuronal cells. In this study, we examined the role RhoG, another member GTPases, nerve growth factor (NGF)-induced PC12 Expression wild-type RhoG cells induced absence NGF, morphology RhoG-expressing was similar that NGF-differentiated Constitutively active RhoG-transfected extended short...

Plexins serve as receptors for repulsive axonal guidance molecules semaphorins. The cytoplasmic domain of the semaphorin 4D (Sema4D) receptor, Plexin-B1 has two separated Ras GTPase-activating protein (GAP)-homologous domains, C1 and C2. Recently, we reported that Rho family small GTPase Rnd1 associates with Plexin-B1, Plexin-B1-Rnd1 complex stimulates activity R-Ras, inducing growth cone collapse in hippocampal neurons response to Sema4D. However, molecular mechanisms by which exhibits GAP...

Plexins, comprising Plexin-A, -B, -C, and -D subfamilies, are receptors for semaphorins governing cell adhesion, migration, axon guidance. Among plexin Plexin-A1 Plexin-B1 have been shown to function as an R-Ras GAP, inducing repulsive responses, the expression of GAP activity requires binding Rnd1, a member Rnd subfamily Rho GTPases. However, signaling pathways Plexin-D1 Plexin-C1 still remain obscure. Here, we found that displayed inhibited migration COS-7 cells, these actions required...

Ferroptosis is an iron-dependent mode of cell death caused by excessive oxidative damage to lipids. Lipid peroxidation normally suppressed glutathione peroxidase 4, which requires reduced glutathione. Cystine a major resource for synthesis, especially in cancer cells. Therefore, cystine deprivation or inhibition uptake promotes ferroptosis However, the roles other molecules involved cysteine deprivation-induced are unexplored. We report here that expression gamma-glutamyltransferase 1...

Plexins are receptors for the axon guidance molecule semaphorins, and several lines of evidence suggest that Rho family small GTPases implicated in downstream signaling Plexins. Recent studies have demonstrated Plexin-B1 activates RhoA induces growth cone collapse through Rho-specific guanine nucleotide exchange factor PDZ-RhoGEF. Here we show Rnd1, a member GTPases, directly interacted with cytoplasmic domain Plexin-B1. In COS-7 cells, coexpression Rnd1 induced cell contraction response to...

Plexins are cell surface receptors for semaphorins and regulate migration in many types. We recently reported that the semaphorin 4D (Sema4D) receptor Plexin-B1 functions as a GTPase-activating protein (GAP) R-Ras, member of Ras family GTPases implicated regulation integrin activity (Oinuma, I., Y. Ishikawa, H. Katoh, M. Negishi. 2004. Science. 305:862–865). characterized role R-Ras downstream Sema4D/Plexin-B1 migration. Activation by Sema4D suppressed ECM-dependent activation,...

Male external genitalia show structural variations among species. Androgenic hormones are essential for the morphological specification of male type copulatory organs, while little is known about developmental mechanisms such secondary sexual characters. Western mosquitofish Gambusia affinis may offer a clue to differentiation researches, because they prominent masculine character appendage development, anal fin gonopodium (GP) transition, and its formation could be induced in early juvenile...

Vertebrates show diverse sexual characters in sexually attractive and reproductive organs, which are regulated by steroid hormones, particularly androgens. However, the evolutionary history of androgen receptor (AR) gene remains largely unknown on basis phylogenic functional analyses. To elucidate diversification AR genes vertebrates, we cloned cDNAs from a shark, basal ray-finned fishes (Actinopterygii), namely bichir sturgeon (Acipenseriformes), teleosts including teleost, arowana...