Most of the known cellular transport machinery involved in biogenesis are ubiquitously expressed and shared between lysosomes and LROs. Examples of common components are the adaptor protein complex-3 AP-3 and biogenesis of lysosome-related organelle complex BLOC These protein complexes control sorting and transport of newly synthesized integral membrane proteins from early endosomes to both lysosomes and LROs such as the melanosome. However, it is unknown what factors cooperate with the ubiquitous transport machinery to mediate transport to LROs in specialized cells.

Focusing on the melanosome, we show that the ubiquitous machinery interacts with cell type-specific Rab proteins, Rab 38 and Rab 32, to facilitate transport to the maturing organelle. Rab and Rab deficient MNT-1 cells displayed abnormal trafficking and steady state levels of known cargoes of the BLOC-2, AP-3, and AP-1 pathways, the melanin-synthesizing enzymes tyrosinase and tyrosinase-related protein - 1. These observations support the idea that Rab 38 and Rab 32 are the specific factors that direct the ubiquitous machinery to mediate transport from early endosomes to maturing LROs.

Additionally, analysis of tyrosinase-related protein-2 and total melanin production indicates that Rab 32 has unique functions that cannot be carried out by Rab 38 in melanosome biogenesis. Ho, Joel R. Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab -interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified.

A systematic literature search identified 61 genes encoding Rab proteins and genes encoding Rab -interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to and 75 tumors. Gene deregulation was analysed with the SAM significant analysis of microarray test or the binomial test.

Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Cluster analysis showed that the RAB 27 gene cluster comprising the genes encoding RAB 27 and its interacting partners was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis.

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This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. The results of this study also demonstrated the involvement of Rab 9A in the regulation of the RUTBC1 localization and in the trafficking of all three melanogenic enzymes. Mahoney, Timothy R. Rab small GTPases are involved in the transport of vesicles between different membranous organelles. RAB -3 is an exocytic Rab that plays a modulatory role in synaptic transmission.

Unexpectedly, mutations in the Caenorhabditis elegans RAB -3 exchange factor homologue, aex-3, cause a more severe synaptic transmission defect as well as a defecation defect not seen in rab -3 mutants. Here, we show that C. We identify aex-6 alleles as containing mutations in rab Interestingly, aex-6 mutants exhibit the same defecation defect as aex-3 mutants. The elongation rate of axons is tightly regulated during development. Recycling of the plasma membrane is known to regulate axon extension; however, the specific molecules involved in recycling within the growth cone have not been fully characterized.

Here, we investigated whether the small GTPases Rab 4 and Rab 5 involved in short-loop recycling regulate the extension of Xenopus retinal axons.

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We report that, in growth cones, Rab 5 and Rab 4 proteins localize to endosomes, which accumulate markers that are constitutively recycled. Fluorescence recovery after photo-bleaching experiments showed that Rab 5 and Rab 4 are recruited to endosomes in the growth cone, suggesting that they control recycling locally. Dynamic image analysis revealed that Rab 4-positive carriers can bud off from Rab 5 endosomes and move to the periphery of the growth cone, suggesting that both Rab 5 and Rab 4 contribute to recycling within the growth cone.

Inhibition of Rab 4 function with dominant-negative Rab 4 or Rab 4 morpholino and constitutive activation of Rab 5 decreases the elongation of retinal axons in vitro and in vivo, but, unexpectedly, does not disrupt axon pathfinding. Thus, Rab 5- and Rab 4-mediated control of endosome trafficking appears to be crucial for axon growth. Collectively, our results suggest that recycling from Rab 5-positive endosomes via Rab 4 occurs within the growth cone and thereby supports axon elongation.

An Installation Commander may adjourn a Commander decides to adjourn the RAB. Federal Register , , , , Non-countermeasure equipped commercial aircraft are at risk during approach and departure due to the large areas around airports that would need to be secured to prevent the use of highly portable and concealable MANPADs. A software model CounterSim has been developed and was used to simulate an SA-7b and large commercial aircraft engagement.

The results of this simulation have found that the threat was lessened when a escort fighter aircraft is flown in the 'Centreline Low' position, or 25 m rearward from the large aircraft and 15 m lower, similar to the Air-to-Air refuelling position. Departure is a particularly vulnerable time for large aircraft due to slow climb rates and the inability to fly evasive manoeuvres. The ESCORT is a bimodal engine capable of supporting a wide range of propulsive thermal and vehicle electrical power requirements. In this mode, the reactor is used to heat a mixture of helium and xenon to drive a closed-loop Brayton cycle in order to generate electrical energy.

The current NASA DRM requires a nuclear thermal propulsion system capable of delivering total mission requirements of N lbf thrust and 50 kWe of spacecraft electrical power. Additionally, these requirements detailed a surface power system capable of providing approximately kW of electrical energy over an approximate 10 year period within a given weight and volume envelope.

A mobile power cart of approximate dimensions 1. The The modifications required to the ESCORT reactor system to support this upgraded electrical power requirements along with operation in the Martian atmospheric conditions are addressed in this paper. Sufficient excess reactivity and burnup capability.

Rab proteins, small GTPases, are key regulators of mammalian Golgi apparatus organization. Based on the effect of Rab activation state, Rab proteins fall into two functional classes. In Class 2, the reverse is true.

We give emphasis to Rab 6, the most abundant Golgi-associated Rab protein. Rab 6 depletion in HeLa cells causes an increase in Golgi cisternal number, longer, more continuous cisternae, and a pronounced accumulation of vesicles; the effect of Rab 6 on Golgi ribbon organization is probably through regulation of vesicle transport. In effector studies, motor proteins and their regulators are found to be key Rab 6 effectors.

A related Rab , Rab 41, affects Golgi ribbon organization in a contrasting manner. The balance between minus- and plus-end directed motor recruitment may well be the major Rab -dependent factor in Golgi ribbon organization. Mukhopadhyay, Amitabha; Barbieri, Alejandro M. To explore the role of GTPases in endocytosis, we developed an assay using Xenopus oocytes injected with recombinant proteins to follow the uptake of the fluid phase marker HRP.

Enhancement of uptake by Rab 7 appears to function via an Rab 5-sensitive pathway in oocytes since the stimulatory effect of Rab 7 was blocked by coinjection of Rab 5:S34N. Our results suggest that Rab 7, while functioning downstream of Rab 5, may be rate limiting for endocytosis in oocytes.

Neurons secrete neuropeptides from dense core vesicles DCVs to modulate neuronal activity.

Little is known about how neurons manage to differentially regulate the release of synaptic vesicles SVs and DCVs. Multiple Rabs and Rab GAPs are typically organized in cascades that confer directionality to membrane-trafficking processes. The functions of these Rabs in Entamoeba have not been determined.

Therefore, as an approach to elucidate the role of the Rab 11 family of GTPases in Entamoeba, immunofluorescence microscopy was undertaken to define the subcellular localization of one member of this family, Eh Rab Under conditions of growth, Eh Rab 11 displayed a punctate pattern in the cytoplasm of trophozoites. Eh Rab 11 did not colocalize with markers for the Golgi apparatus, endoplasmic reticulum, pinosomes, phagosomes, or compartments formed by receptor-mediated endocytosis, suggesting that this Rab may not play a role in vesicle trafficking between these organelles.

Under conditions of iron and serum starvation, Eh Rab 11 was translocated to the periphery of the cell. The altered cellular localization was accompanied by multinucleation of the cells as well as the acquisition of detergent resistance by the cells, features that are characteristic of Entamoeba cysts. The translocation of Eh Rab 11 to the periphery of the cell during iron and serum starvation was specific as the subcellular localizations of two other Rab GTPases, Eh Rab 7 and Eh Rab A, were not altered under the same conditions.

In addition, the formation of multinucleated cells by inhibition of cytokinesis was not sufficient to induce the translocation of Eh Rab 11 to the cell periphery. Taken together, the data suggest that iron and serum starvation may induce encystation in E. Moreover, these studies are the first to describe a putative role for a Rab GTPase in encystation in Entamoeba sp. These vesicles were known to originate from the Golgi and contain secreted or membrane proteins.

Published by The Company of Biologists Ltd. The depletion of pkaap also had a direct effect on Rab 11 vesicle exocytosis and the secretion of the antimicrobial peptide Drosomycin at the plasma membrane. We propose that Pkaap has a dual role in antimicrobial peptide traffic and exocytosis, making it an essential component for the secretion of inflammatory mediators and the defence of the host against pathogens.

Hoogenraad, Casper C. The endosomal pathway in neuronal dendrites is essential for membrane receptor trafficking and proper synaptic function and plasticity. However, the molecular mechanisms that organize specific endocytic trafficking routes are poorly understood. Here, we identify GRIP-associated protein - 1 GRASP-1 as a neuron-specific effector of Rab 4 and key component of the molecular machinery that coordinates recycling endosome maturation in dendrites.

The data uncover a new mechanism to achieve specificity and directionality in neuronal membrane receptor trafficking. Wnt6 maintains anterior escort cells as an integral component of the germline stem cell niche. In Drosophila ovaries, germline stem cells depend on cap cells for self-renewing signals and physical attachment.

Germline stem cells also contact the anterior escort cells, and here we report that anterior escort cells are absolutely required for germline stem cell maintenance. When escort cells die from impaired Wnt signaling or hid expression, the loss of anterior escort cells causes loss of germline stem cells.

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Anterior escort cells function as an integral niche component by promoting DE-cadherin anchorage and by transiently expressing the Dpp ligand to promote full-strength BMP signaling in germline stem cells. Anterior escort cells are maintained by Wnt6 ligands produced by cap cells; without Wnt6 signaling, anterior escort cells die leaving vacancies in the niche, leading to loss of germline stem cells.

Our data identify anterior escort cells as constituents of the germline stem cell niche, maintained by a cap cell-produced Wnt6 survival signal. Stem cells reside in a niche, a local environment whose cellular and molecular complexity is still being elucidated. In this study, we investigate which Rab 7 effectors mediate this effect. To evaluate current level of safety under the care of an escort following intravenous sedation, post-sedation arrangements and to identify potential risk levels. Information and post-sedation arrangements are important to patients'safety following surgery but although there is a general consensus over what is recommended for patients and their escorts , there is little, if any, literature on the escorts ' awareness of sedation and accordance to post-sedation arrangement and recommendations.

Escorts of consecutive patients treated in oral surgery under sedation midazolam completed a questionnaire composed of 27 questions divided into seven sections including demographics, awareness of sedation, source of information and post-operative arrangement. From the data collected, two scores were calculated representative of the escorts ' Safety and Reliability.

Safety scores were statistically correlated with instruction source while Reliability correlated to a wider variety of parameters including gender, age as well as information source. Provision of clear written information to escorts is recommended as likely to improve patients' safety.

Assessment of escorts ' Safety and Reliability could provide a means for improving quality and safety of sedation service. Strict spatiotemporal control of trafficking events between organelles is critical for maintaining homeostasis and directing cellular responses. This regulation is particularly important in immune cells for mounting specialized immune defenses. By controlling the formation, transport and fusion of intracellular organelles, Rab GTPases serve as master regulators of membrane trafficking.

In this review, we discuss the cellular and molecular mechanisms by which Rab GTPases regulate immunity and inflammation.