Differential Regulation of Rab GTPase Expression in Monocyte-Derived Dendritic Cells upon Lipopolysaccharide Activation: A Correlation to Maturation-Dependent Functional Properties

Berg-Larsen, Axel; Landsverk, Ole J. B.; Progida, Cinzia; Gregers, Tone F.; Bakke, Oddmund

doi:10.1371/journal.pone.0073538

Cited by 10 publications

(16 citation statements)

References 90 publications

(109 reference statements)

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“…This notion is based on the classical or revised hematopoietic hierarchy model, which describes a stepwise differentiation of HSCs via intermediate progenitors into mature cells. However, recent studies have suggested a continuous model that describes heterogeneity of HSCs gradually acquire well-balanced cell groups under physiological conditions 14,15 . In this model, there are no obvious boundaries between different hierarchical levels of hematopoietic cells 14 .…”

Section: Discussionmentioning

confidence: 99%

Expression and localisation of Rab44 in immune-related cells change during cell differentiation and stimulation

Tokuhisa

Kadowaki

Ogawa

et al. 2020

Sci Rep

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Rab44 is a large Rab GTPase that contains a Rab-GTPase domain and some additional domains, such as EF-hand and coiled-coil domains at the N-terminus. Our previous study showed that Rab44 negatively regulates osteoclast differentiation by modulating intracellular calcium levels; however, aside from those findings, there is little information concerning Rab44 on other cells or tissues. In this study, we showed that Rab44 was highly expressed in bone marrow cells among various mouse tissues. Immunohistochemical studies indicated that Rab44 was detectable by only a small number of cells in the immune-related tissues and that Rab44 was partially detected in CD117-positive cells, but not in Stem cell antigen 1-positive cells in the bone marrow. Rab44 expression levels were decreased during differentiation of immune-related cells, such as neutrophils, macrophages, and dendritic cells compared with bone marrow cells. Although endogenous Rab44 in macrophages was localised in lysosomes, lipopolysaccharide (LPS) stimulation led to partial translocation to early endosomes and the plasma membrane. Moreover, Rab44 expression levels were altered by treatment with various immunomodulators, including LPS. These results indicate that Rab44 expression and localisation in bone marrow cells and macrophages alters with cell differentiation and stimulation. Rab GTPases are critical regulators of intracellular membrane trafficking, including vesicle transport, membrane fission, tethering, docking, and fusion events 1,2. Rab GTPases coordinate membrane trafficking as molecular switches that change conformational states between active GTP-bound and inactive GDP-bound forms 3. At present, there are 66 Rab genes in the human genome 4,5. Each Rab GTPase localises to a distinct membrane compartment to modulate membrane trafficking. Among various Rab GTPases, Rab1, Rab5, Rab6, Rab7, and Rab11 are known as 'housekeeping Rabs' , since they are conserved from yeast to humans 6. Meanwhile, most other Rabs have unique cell type-specific or tissue-specific roles. For example, Rab3 and Rab27 members are termed as 'secretory Rabs' that are predominantly localised in neurons and endocrine cells that have unique vesicles for regulatory secretion 7. In contrast to these well-characterised Rabs, the cellular function of Rab44 is poorly investigated. Rab44 is a large Rab GTPase that encodes several domains, such as the EF-hand domain, coiled-coil domain, and Rab-GTPase domain 8. The amino acid sequences of human Rab44 indicate a putative molecular mass of approximately 110 kDa. Considering that Rab 1-43 are the monomeric small GTPases with molecular weights of about 20-30 kDa, Rab44 is an atypical Rab GTPase of approximately 75-150 kDa. Recently, our research group has discovered that Rab44 expression is transiently upregulated during osteoclast differentiation 9. Moreover, knockdown of Rab44 promotes osteoclast differentiation, whereas overexpression of Rab44 prevents it. Rab44 overexpressed in macrophages is predominantly localised in the Golgi complex a...

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Section: Discussionmentioning

confidence: 99%

Expression and localisation of Rab44 in immune-related cells change during cell differentiation and stimulation

Tokuhisa

Kadowaki

Ogawa

et al. 2020

Sci Rep

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“…HeLa cells were transfected with siRNA (90 nM) using Oligofectamine (Life Technologies) for 72 h, replated, and left for another 48 h before further experiments were performed. To ascertain degree of silencing, western blotting was carried out as previously described . For immunolabeling, the following antibodies were used: anti‐tubulin (Zymed), anti‐Rab9 (ab2810, Abcam) and anti‐p40 (ab137691, Abcam).…”

Section: Methodsmentioning

confidence: 99%

Spatiotemporal Resolution of Rab9 and CI‐MPR Dynamics in the Endocytic Pathway

Kucera

Distefano

Berg-Larsen

et al. 2016

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Rab9 is a small GTPase that localizes to the trans-Golgi Network (TGN) and late endosomes. Its main function has long been connected to the recycling of mannose-6-phosphate receptors (MPRs). However, recent studies link Rab9 also to autophagy and lysosome biogenesis. In this paper, using confocal imaging, we characterize for the first time the live dynamics of the Rab9 constitutively active mutant, Rab9Q66L. We find that it localizes predominantly to late endosomes and that its expression in HeLa cells disperses TGN46 and cation-independent (CI-MPR) away from the Golgi yet, has no effect on the retrograde transport of CI-MPR. We also show that CI-MPR and Rab9 enter the endosomal pathway together at the transition stage between early, Rab5-positive, and late, Rab7a-positive, endosomes. CI-MPR localizes transiently to separate domains on these endosomes, where vesicles carrying CI-MPR attach and detach within seconds. Taken together, our results demonstrate that Rab9 mediates the delivery of CI-MPR to the endosomal pathway, entering the maturing endosome at the early-to-late transition.

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“…For example, Rab7b is highly expressed in immune cells such as dendritic cells and shows highly variable expression levels during differentiation (Berg-Larsen et al, 2013;Progida et al, 2010). Conversely, another Rab protein, Rab31 (also known as Rab22b) is highly expressed in brain tissue (Ng et al, 2009).…”

Section: Other Rabsmentioning

confidence: 99%

Bidirectional traffic between the Golgi and the endosomes – machineries and regulation

Progida

Bakke

2016

Journal of Cell Science

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The bidirectional transport between the Golgi complex and the endocytic pathway has to be finely regulated in order to ensure the proper delivery of newly synthetized lysosomal enzymes and the return of sorting receptors from degradative compartments. The high complexity of these routes has led to experimental difficulties in properly dissecting and separating the different pathways. As a consequence, several models have been proposed during the past decades. However, recent advances in our understanding of endosomal dynamics have helped to unify these different views. We provide here an overview of the current insights into the transport routes between Golgi and endosomes in mammalian cells. The focus of the Commentary is on the key molecules involved in the trafficking pathways between these intracellular compartments, such as Rab proteins and sorting receptors, and their regulation. A proper understanding of the bidirectional traffic between the Golgi complex and the endolysosomal system is of uttermost importance, as several studies have demonstrated that mutations in the factors involved in these transport pathways result in various pathologies, in particular lysosome-associated diseases and diverse neurological disorders, such as Alzheimer's and Parkinson's disease.

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Differential Regulation of Rab GTPase Expression in Monocyte-Derived Dendritic Cells upon Lipopolysaccharide Activation: A Correlation to Maturation-Dependent Functional Properties

Cited by 10 publications

References 90 publications

Expression and localisation of Rab44 in immune-related cells change during cell differentiation and stimulation

Expression and localisation of Rab44 in immune-related cells change during cell differentiation and stimulation

Spatiotemporal Resolution of Rab9 and CI‐MPR Dynamics in the Endocytic Pathway

Bidirectional traffic between the Golgi and the endosomes – machineries and regulation

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