ADP-Ribosylation Factor Family of Small GTP-Binding Proteins: Their Membrane Recruitment, Activation, Crosstalk and Functions

Li, Tiantian; Guo, Yusong

doi:10.3389/fcell.2022.813353

Cited by 9 publications

(4 citation statements)

References 70 publications

(101 reference statements)

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“…During starvation, genes related to development ( cotC, cotD, cotE ) were significantly downregulated in cln5 - cells. In contrast, genes encoding ADP-ribosylation factors ( arrJ, arrH, arrK ), which modulate the trafficking of endocytic and secretory vesicles, and ponticulin-like proteins ( ponC1, ponC2, ponC3, ponC4, ponC5 ), which are involved in actin bundling and cell-cell adhesion, were the most significantly upregulated genes in cln5 -deficient cells ( Ingalls et al, 1989 ; Shariff and Luna, 1990 ; Chia et al, 1993 ; Li and Guo, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

An altered transcriptome underlies cln5-deficiency phenotypes in Dictyostelium discoideum

Kim

Huber

2022

Front. Genet.

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Mutations in CLN5 cause a subtype of neuronal ceroid lipofuscinosis (NCL) called CLN5 disease. The NCLs, commonly referred to as Batten disease, are a family of neurodegenerative lysosomal storage diseases that affect all ages and ethnicities globally. Previous research showed that CLN5 participates in a variety of cellular processes. However, the precise function of CLN5 in the cell and the pathway(s) regulating its function are not well understood. In the model organism Dictyostelium discoideum, loss of the CLN5 homolog, cln5, impacts various cellular and developmental processes including cell proliferation, cytokinesis, aggregation, cell adhesion, and terminal differentiation. In this study, we used comparative transcriptomics to identify differentially expressed genes underlying cln5-deficiency phenotypes during growth and the early stages of multicellular development. During growth, genes associated with protein ubiquitination/deubiquitination, cell cycle progression, and proteasomal degradation were affected, while genes linked to protein and carbohydrate catabolism were affected during early development. We followed up this analysis by showing that loss of cln5 alters the intracellular and extracellular amounts of proliferation repressors during growth and increases the extracellular amount of conditioned medium factor, which regulates cAMP signalling during the early stages of development. Additionally, cln5- cells displayed increased intracellular and extracellular amounts of discoidin, which is involved in cell-substrate adhesion and migration. Previous work in mammalian models reported altered lysosomal enzyme activity due to mutation or loss of CLN5. Here, we detected altered intracellular activities of various carbohydrate enzymes and cathepsins during cln5- growth and starvation. Notably, cln5- cells displayed reduced β-hexosaminidase activity, which aligns with previous work showing that D. discoideum Cln5 and human CLN5 can cleave the substrate acted upon by β-hexosaminidase. Finally, consistent with the differential expression of genes associated with proteasomal degradation in cln5- cells, we also observed elevated amounts of a proteasome subunit and reduced proteasome 20S activity during cln5- growth and starvation. Overall, this study reveals the impact of cln5-deficiency on gene expression in D. discoideum, provides insight on the genes and proteins that play a role in regulating Cln5-dependent processes, and sheds light on the molecular mechanisms underlying CLN5 disease.

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Section: Resultsmentioning

confidence: 99%

An altered transcriptome underlies cln5-deficiency phenotypes in Dictyostelium discoideum

Kim

Huber

2022

Front. Genet.

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“…Arfs (ADP ribosylation factors) are subfamilies of small GTP-binding proteins with low molecular weight and can bind to guanine nucleotides involved in vital intracellular processes, including signal transduction ( Liu et al., 2017 ) and vesicle trafficking ( Li and Guo, 2022 ). Arfs are classified into three types: type I (Arf1-3), type II (Arf4-5), and type III (Arf6).…”

Section: Effectors Specific For Rickettsia Spp Of Tgmentioning

confidence: 99%

Subversion of host cell signaling: The arsenal of Rickettsial species

Huang

Luo²,

Ouyang³

et al. 2022

Front. Cell. Infect. Microbiol.

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Rickettsia is a genus of nonmotile, Gram-negative, non-spore-forming, highly pleomorphic bacteria that cause severe epidemic rickettsioses. The spotted fever group and typhi group are major members of the genus Rickettsia. Rickettsial species from the two groups subvert diverse host cellular processes, including membrane dynamics, actin cytoskeleton dynamics, phosphoinositide metabolism, intracellular trafficking, and immune defense, to promote their host colonization and intercellular transmission through secreted effectors (virulence factors). However, lineage-specific rickettsiae have exploited divergent strategies to accomplish such challenging tasks and these elaborated strategies focus on distinct host cell processes. In the present review, we summarized current understandings of how different rickettsial species employ their effectors’ arsenal to affect host cellular processes in order to promote their own replication or to avoid destruction.

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“…Moreover, of the 17 GEF and 23 GAP proteins, many of these share the ability to modulate nucleotide association on most ARFs in vitro . ARF GTPases can also act in amplifying loops, with a GEF acting as an ARF-GTP effector to activate further ARFs 7, 8 . This complexity makes it difficult to predict how ARFs and their regulators contribute to cellular behaviour from individual single interactions and sets the stage for a systems-level analysis to identify how these potentially overlapping components functionally contribute to morphogenesis.…”

Section: Mainmentioning

confidence: 99%

The small GTPase ARF3 controls metastasis and invasion modality by regulating N-cadherin levels

Sandilands

Freckmann

Román-Fernández

et al. 2022

Preprint

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ARF GTPases are central regulators of membrane trafficking that act by controlling local membrane identity and remodelling to facilitate vesicle formation. Unravelling ARF GTPase function is complicated by the overlapping association of ARFs with guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and numerous interactors. The extent to which redundancy is a major factor in ARF function or whether individual ARF GTPases make unique contributions to cellular behaviour remains unclear. Through a functional genomic screen of 3-Dimensional (3D) prostate cancer cell behaviour we explore the contribution of all known ARF GTPases, GEFs, GAPs, and a large selection of interactors to collective morphogenesis. This revealed that the ARF3 GTPase regulates the modality of invasion, acting as a switch between leader cell-led chains of invasion or collective sheet movement. Functionally, the ability of ARF3 to control invasion modality is dependent on association and subsequent control of the junctional adhesion molecule N-cadherin. In vivo, ARF3 levels acted as a rheostat for metastasis from intraprostatic tumour transplants and ARF3:N-cadherin expression can be used to identify prostate cancer patients with metastatic, poor-outcome disease. Our analysis defines a unique function for the ARF3 GTPase in controlling how cells collectively organise during invasion and metastasis.

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ADP-Ribosylation Factor Family of Small GTP-Binding Proteins: Their Membrane Recruitment, Activation, Crosstalk and Functions

Cited by 9 publications

References 70 publications

An altered transcriptome underlies cln5-deficiency phenotypes in Dictyostelium discoideum

An altered transcriptome underlies cln5-deficiency phenotypes in Dictyostelium discoideum

Subversion of host cell signaling: The arsenal of Rickettsial species

The small GTPase ARF3 controls metastasis and invasion modality by regulating N-cadherin levels

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