scholarly journals Multitasking Rab Proteins in Autophagy and Membrane Trafficking: A Focus on Rab33b

2019 ◽  
Vol 20 (16) ◽  
pp. 3916 ◽  
Author(s):  
Niamh E. Morgan ◽  
Meritxell B. Cutrona ◽  
Jeremy C. Simpson
Keyword(s):  
Golgi Apparatus ◽  
Membrane Trafficking ◽  
Molecular Basis ◽  
Current Knowledge ◽  
Energy Levels ◽  
Degradation Process ◽  
Eukaryotic Cells ◽  
Rab Proteins ◽  
Gtp Binding ◽  
Skeletal Disorder

Autophagy (particularly macroautophagy) is a bulk degradation process used by eukaryotic cells in order to maintain adequate energy levels and cellular homeostasis through the delivery of long-lived proteins and organelles to the lysosome, resulting in their degradation. It is becoming increasingly clear that many of the molecular requirements to fulfil autophagy intersect with those of conventional and unconventional membrane trafficking pathways. Of particular interest is the dependence of these processes on multiple members of the Rab family of small GTP binding proteins. Rab33b is a protein that localises to the Golgi apparatus and has suggested functions in both membrane trafficking and autophagic processes. Interestingly, mutations in the RAB33B gene have been reported to cause the severe skeletal disorder, Smith–McCort Dysplasia; however, the molecular basis for Rab33b in this disorder remains to be determined. In this review, we focus on the current knowledge of the participation of Rab33b and its interacting partners in membrane trafficking and macroautophagy, and speculate on how its function, and dysfunction, may contribute to human disease.

scholarly journals Identification of rab2 as a tubulovesicle-membrane-associated protein in rabbit gastric parietal cells

1992 ◽  
Vol 285 (3) ◽  
pp. 715-719 ◽  
Author(s):  
L H Tang ◽  
S A Stoch ◽  
I M Modlin ◽  
J R Goldenring
Keyword(s):  
Membrane Trafficking ◽  
Integral Membrane Protein ◽  
Binding Activity ◽  
Parietal Cells ◽  
Amino Acid Difference ◽  
Rab Proteins ◽  
Human Sequence ◽  
Subcellular Membrane ◽  
Gtp Binding ◽  
Gastric Parietal Cells

Rab proteins, which are ras-like low-molecular-mass GTP-binding proteins, are postulated to act as specific regulators of membrane trafficking in exocytosis and endocytosis. Previously, we reported a 23 kDa tubulovesicle-associated GTP-binding protein in rabbit gastric parietal cells [Basson, Goldenring, Tang, Lewis, Padfield, Jamieson & Modlin (1991) Biochem. J. 279, 43-48]. The major component of the 23 kDa protein is now identified as rab2. Rab2 was co-localized in tubulovesicle membranes from parietal cells. Consistent with GTP-binding activity (as documented before), upon maximal stimulation of parietal cells, rab2 immunoreactivity was redistributed from a 50,000 g to a 4000 g subcellular membrane fraction. The tubulovesicle-associated rab2 behaved as an integral membrane protein, since both 0.5 M-NaCl and 0.1 M-carbonate extraction failed to remove the protein from the tubulovesicle membrane. Utilizing a PCR the rab2 cDNA sequence from rabbit parietal cells was obtained, and it showed only one amino acid difference compared with the human sequence. The results of the present study provide strong evidence that parietal cells possess a rab2 protein which is tightly associated with tubulovesicle membranes.

Targeting of Rab GTPases to cellular membranes

2005 ◽  
Vol 33 (4) ◽  
pp. 652-656 ◽  
Author(s):  
B.R. Ali ◽  
M.C. Seabra
Keyword(s):  
Membrane Trafficking ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Small Gtpases ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Cellular Membranes ◽  
Structural Determinants ◽  
Cellular Processes

Rab proteins are members of the superfamily of Ras-like small GTPases and are involved in several cellular processes relating to membrane trafficking and organelle mobility throughout the cell. Like other small GTPases, Rab proteins are initially synthesized as soluble proteins and for membrane attachment they require the addition of lipid moiety(ies) to specific residues of their polypeptide chain. Despite their well-documented roles in regulating cellular trafficking, Rab proteins own trafficking is still poorly understood. We still need to elucidate the molecular mechanisms of their recruitment to cellular membranes and the structural determinants for their specific cellular localization. Recent results indicate that Rab cellular targeting might be Rab-dependent, and this paper briefly reviews our current knowledge of this process.

scholarly journals The small GTP-binding protein rab6p is distributed from medial Golgi to the trans-Golgi network as determined by a confocal microscopic approach

1992 ◽  
Vol 103 (3) ◽  
pp. 785-796 ◽  
Author(s):  
C. Antony ◽  
C. Cibert ◽  
G. Geraud ◽  
A. Santa Maria ◽  
B. Maro ◽  
...  
Keyword(s):  
Golgi Apparatus ◽  
G Protein ◽  
Cell Lines ◽  
Binding Protein ◽  
Rab Proteins ◽  
Gtp Binding Protein ◽  
Trans Golgi Network ◽  
Gtp Binding ◽  
Golgi Network ◽  
Exocytic Pathway

A key role in the regulation of membrane traffic is played by the rab proteins, members of a family of ras-related small GTP-binding proteins. This family comprises at least 25 identified members, the intracellular localization of only a few of which has been investigated. rab6p has been shown to be distributed along the exocytic pathway in association with the medial and trans regions of the Golgi apparatus. A confocal laser scanning microscopic (CLSM) approach coupled with image analysis was used to compare the localization of rab6p with selected reference Golgi markers by double immunofluorescence on culture cell lines. CLSM analysis shows that, under a set of well-defined conditions, one can investigate the possible colocalization of known markers of Golgi compartments and orientate a couple of labeled Golgi antigens with regard to the polarity of the Golgi apparatus. Thus, having validated the CLSM analysis, the localization of rab6p was studied and compared with some of these markers and the VSV-G protein in VSV (vesicular stomatitis virus)-infected cells blocked at 20 degrees C. rab6p is shown to be associated in all the cell lines used with the last cisternae of the Golgi apparatus and particularly with the trans-Golgi network (TGN), the site of protein sorting at the exit of the Golgi apparatus. These results were supported by an electron microscopic study using double-immunolabeled cryosections: rab6p was found in some flat cisternae of the Golgi stack and colocalized with the VSV-G protein in the TGN. Our results show that the small GTP-binding protein rab6p is distributed from medial Golgi to TGN along the exocytic pathway.

scholarly journals Liquid–liquid phase separation in human health and diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Bin Wang ◽  
Lei Zhang ◽  
Tong Dai ◽  
Ziran Qin ◽  
Huasong Lu ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Human Health ◽  
Essential Role ◽  
Current Knowledge ◽  
Vital Role ◽  
Liquid Phase Separation ◽  
Eukaryotic Cells ◽  
Liquid Liquid Phase Separation

AbstractEmerging evidence suggests that liquid–liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences that indicate that LLPS plays a vital role in human health and diseases. In this review, we describe our current understanding of LLPS and summarize its physiological functions. We further describe the role of LLPS in the development of human diseases. Additionally, we review the recently developed methods for studying LLPS. Although LLPS research is in its infancy—but is fast-growing—it is clear that LLPS plays an essential role in the development of pathophysiological conditions. This highlights the need for an overview of the recent advances in the field to translate our current knowledge regarding LLPS into therapeutic discoveries.

Mammalian mitochondrial translation — revealing consequences of divergent evolution

2019 ◽  
Vol 47 (5) ◽  
pp. 1429-1436 ◽  
Author(s):  
Rawaa A. Z. Al-Faresi ◽  
Robert. N. Lightowlers ◽  
Zofia M. A. Chrzanowska-Lightowlers
Keyword(s):  
Common Ancestor ◽  
Current Knowledge ◽  
Eukaryotic Cells ◽  
Divergent Evolution ◽  
Mitochondrial Translation ◽  
Complete Understanding ◽  
Genetic Origin ◽  
Cryo Electron Microscopy ◽  
Encoded Proteins ◽  
Molecular Aspects

Abstract Mitochondria are ubiquitous organelles present in the cytoplasm of all nucleated eukaryotic cells. These organelles are described as arising from a common ancestor but a comparison of numerous aspects of mitochondria between different organisms provides remarkable examples of divergent evolution. In humans, these organelles are of dual genetic origin, comprising ∼1500 nuclear-encoded proteins and thirteen that are encoded by the mitochondrial genome. Of the various functions that these organelles perform, it is only oxidative phosphorylation, which provides ATP as a source of chemical energy, that is dependent on synthesis of these thirteen mitochondrially encoded proteins. A prerequisite for this process of translation are the mitoribosomes. The recent revolution in cryo-electron microscopy has generated high-resolution mitoribosome structures and has undoubtedly revealed some of the most distinctive molecular aspects of the mitoribosomes from different organisms. However, we still lack a complete understanding of the mechanistic aspects of this process and many of the factors involved in post-transcriptional gene expression in mitochondria. This review reflects on the current knowledge and illustrates some of the striking differences that have been identified between mitochondria from a range of organisms.

Mechanisms of Giardia lamblia differentiation into cysts

1997 ◽  
Vol 61 (3) ◽  
pp. 294-304
Author(s):  
H D Luján ◽  
M R Mowatt ◽  
T E Nash
Keyword(s):  
Giardia Lamblia ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Life Cycles ◽  
Eukaryotic Cells ◽  
Organelle Biogenesis ◽  
Adaptive Responses ◽  
Specific Stimulus ◽  
Adverse Conditions

Microbiologists have long been intrigued by the ability of parasitic organisms to adapt to changes in the environment. Since most parasites occupy several niches during their journey between vectors and hosts, they have developed adaptive responses which allow them to survive under adverse conditions. Therefore, the life cycles of protozoan and helminthic parasites are excellent models with which to study numerous mechanisms involved in cell differentiation, such as the regulation of gene expression, signal transduction pathways, and organelle biogenesis. Unfortunately, many of these studies are very difficult because the conditions needed to elicit developmental changes in parasites remain undetermined in most cases. Recently, several interesting findings were reported on the process of differentiation of Giardia lamblia trophozoites into cysts. G. lamblia is a flagellated protozoan that inhabits the upper small intestine of its vertebrate host and is a major cause of enteric disease worldwide. It belongs to the earliest identified lineage among eukaryotes and therefore offers a unique insight into the progression from primitive to more complex eukaryotic cells. The discovery of a specific stimulus that induces trophozoites to differentiate into cysts, the identification and characterization of encystation-specific molecules, the elucidation of novel biochemical pathways, and the development of useful reagents and techniques have made this parasite an excellent model with which to study differentiation in eukaryotic cells. In this review, we summarize the most recent fundings on several aspects of Giardia differentiation and discuss the significance of these findings within the context of current knowledge in the field.

scholarly journals A Phytophthora capsici RXLR effector manipulates plant immunity by targeting RAB proteins and disturbing vesicle-mediated protein trafficking pathway

2021 ◽  
Author(s):  
Tianli Li ◽  
Gan Ai ◽  
Xiaowei Fu ◽  
Jin Liu ◽  
Hai Zhu ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Plant Immunity ◽  
Phytophthora Capsici ◽  
Functional Characterization ◽  
Ectopic Expression ◽  
Defense Responses ◽  
Infection Process ◽  
Small Gtpase ◽  
Rab Proteins ◽  
Rxlr Effector

The oomycete pathogen Phytophthora capsici encodes hundreds of RXLR effectors to enter plant cells and suppress host defense responses. Only few of them are conserved across different strains and species. Such ‘core effectors’ may target hub immunity pathways that are essential during Phytophthora pathogens interacting with their hosts. However, the underlying mechanisms of core RXLRs-mediated host immunity manipulation are largely unknown. Here, we report the functional characterization of a P. capsici RXLR effector, RXLR242. RXLR242 expression is highly induced during the infection process. Its ectopic expression in Nicotiana benthamiana promotes Phytophthora infection. RXLR242 physically interacts with a group of RAB proteins, which belong to the small GTPase family and function in specifying transport pathways in the intracellular membrane trafficking system. RXLR242 impedes the secretion of PATHOGENESIS-RELATED 1 (PR1) protein to the apoplast by interfering the formation of RABE1-7-labeled vesicles. Further analysis indicated that such phenomenon is resulted from competitive binding of RXLR242 to RABE1-7. RXLR242 also interferes trafficking of the membrane-located receptor FLAGELLIN-SENSING 2 (FLS2) through competitively interacting with RABA4-3. Taken together, our work demonstrates that RXLR242 manipulates plant immunity by targeting RAB proteins and disturbing vesicle-mediated protein transporting pathway in plant hosts.

Crystal structure of the GTP-binding protein-like domain of AGAP1

2021 ◽  
Vol 77 (4) ◽  
Author(s):  
Nuo Cheng ◽  
Hao Zhang ◽  
Shiyan Zhang ◽  
Xiaodan Ma ◽  
Guoyu Meng
Keyword(s):  
Membrane Trafficking ◽  
Protein Transport ◽  
Structural Information ◽  
Binding Protein ◽  
Lymphoblastic Leukemia ◽  
Diffusion Method ◽  
Gtp Binding Protein ◽  
Aberrant Expression ◽  
Cell Parameters ◽  
Gtp Binding

AGAP1 is often considered to regulate membrane trafficking, protein transport and actin cytoskeleton dynamics. Recent studies have shown that aberrant expression of AGAP1 is associated with many diseases, including neurodevelopmental disorders and acute lymphoblastic leukemia. It has been proposed that the GTP-binding protein-like domain (GLD) is involved in the binding of cofactors and thus regulates the catalytic activity of AGAP1. To obtain a better understanding of the pathogenic mechanism underpinning AGAP1-related diseases, it is essential to obtain structural information. Here, the GLD (residues 70–235) of AGAP1 was overexpressed in Escherichia coli BL21 (DE3) cells. Affinity and gel-filtration chromatography were used to obtain AGAP1GLD with high purity for crystallization. Using the hanging-drop vapor-diffusion method with the protein at a final concentration of 20 mg ml−1, AGAP1GLD protein crystals of suitable size were obtained. The crystals were found to diffract to 3.0 Å resolution and belonged to space group I4, with unit-cell parameters a = 100.39, b = 100.39, c = 48.08 Å. The structure of AGAP1GLD exhibits the highly conserved functional G1–G5 loops and is generally similar to other characterized ADP-ribosylation factor (Arf) GTPase-activating proteins (GAPs), implying an analogous function to Arf GAPs. Additionally, this study indicates that AGAP1 could be classified as a type of NTPase, the activity of which might be regulated by protein partners or by its other domains. Taken together, these results provide insight into the regulatory mechanisms of AGAP1 in cell signaling.

scholarly journals Local Secretory Trafficking Pathways in Neurons and the Role of Dendritic Golgi Outposts in Different Cell Models

2020 ◽  
Vol 13 ◽  
Author(s):  
Jingqi Wang ◽  
Lou Fourriere ◽  
Paul A. Gleeson
Keyword(s):  
Cell Body ◽  
Membrane Trafficking ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Model Organisms ◽  
Neuronal Structure ◽  
Anterograde Transport ◽  
Transport Pathways ◽  
Human Neurons

A fundamental characteristic of neurons is the relationship between the architecture of the polarized neuron and synaptic transmission between neurons. Intracellular membrane trafficking is paramount to establish and maintain neuronal structure; perturbation in trafficking results in defects in neurodevelopment and neurological disorders. Given the physical distance from the cell body to the distal sites of the axon and dendrites, transport of newly synthesized membrane proteins from the central cell body to their functional destination at remote, distal sites represents a conundrum. With the identification of secretory organelles in dendrites, including endoplasmic reticulum (ER) and Golgi outposts (GOs), recent studies have proposed local protein synthesis and trafficking distinct from the conventional anterograde transport pathways of the cell body. A variety of different model organisms, including Drosophila, zebrafish, and rodents, have been used to probe the organization and function of the local neuronal secretory network. Here, we review the evidence for local secretory trafficking pathways in dendrites in a variety of cell-based neuronal systems and discuss both the similarities and differences in the organization and role of the local secretory organelles, especially the GOs. In addition, we identify the gaps in the current knowledge and the potential advances using human induced pluripotent stem cells (iPSCs) in defining local membrane protein trafficking in human neurons and in understanding the molecular basis of neurological diseases.

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