Multiple Roles of Rab GTPases at the Golgi

Progida, Cinzia

doi:10.1007/978-3-030-23173-6_6

Cited by 8 publications

(10 citation statements)

References 214 publications

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“…Rab GTPases play key regulatory roles in intracellular vesicular trafficking [1,2,[4][5][6]. Like other small GTPases, Rab proteins exist in two forms, an active GTP-bound state that is necessary for trafficking of cellular cargo and an inactive GDP-bound state [1,3].…”

Section: Discussionmentioning

confidence: 99%

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Noncanonical Rab9a action supports endosomal exit of human papillomavirus during virus entry

Choi

DiMaio

2023

Preprint

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Rab GTPases play key roles in controlling intracellular vesicular transport. GTP-bound Rab proteins support vesicle trafficking. Here, we report that, unlike cellular protein cargos, the delivery of human papillomaviruses (HPV) into the retrograde transport pathway during virus entry is inhibited by Rab9a in its GTP-bound form. Knockdown of Rab9a hampers HPV entry by regulating the HPV-retromer interaction and impairing retromer-mediated endosome-to-Golgi transport of the incoming virus, resulting in the accumulation of HPV in the endosome. Rab9a is in proximity to HPV as early as 3.5 h post-infection, prior to the Rab7-HPV interaction. HPV displays increased association with retromer in Rab9a knockdown cells, even in the presence of dominant negative Rab7. Thus, Rab9a can regulate HPV-retromer association independently of Rab7. Surprisingly, excess GTP-Rab9a impairs HPV entry, whereas excess GDP-Rab9a stimulates entry. These findings reveal that HPV employs a trafficking mechanism distinct from that used by cellular proteins.

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Section: Discussionmentioning

confidence: 99%

“…Rab GTPases are key regulators of intracellular vesicular transport [1][2][3]. In general, when bound to guanosine triphosphate (GTP), Rab proteins are active and support vesicle trafficking, but they do not support vesicle transport when bound to guanosine diphosphate (GDP) [1,3].…”

Section: Introductionmentioning

confidence: 99%

Noncanonical Rab9a action supports endosomal exit of human papillomavirus during virus entry

Choi

DiMaio

2023

Preprint

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“…Rab-GTPases have long been known to localise to the Golgi complex ( Martinez et al, 1994 ; Progida, 2019 ; Westrate et al, 2020 ). By cycling between their GTP-loaded active and GDP-loaded inactive states, Rabs spatiotemporally coordinate the recruitment of effectors to execute the various steps of Golgi cisternal progression and maturation.…”

Section: Small Gtpases As Molecular Switches Of Cisternal Maturationmentioning

confidence: 99%

Role of the Mosaic Cisternal Maturation Machinery in Glycan Synthesis and Oncogenesis

Sahu

Balakrishnan

Martino

et al. 2022

Front. Cell Dev. Biol.

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Tumorigenesis is associated with the deregulation of multiple processes, among which the glycosylation of lipids and proteins is one of the most extensively affected. However, in most cases, it remains unclear whether aberrant glycosylation is a cause, a link in the pathogenetic chain, or a mere consequence of tumorigenesis. In other cases, instead, studies have shown that aberrant glycans can promote oncogenesis. To comprehend how aberrant glycans are generated it is necessary to clarify the underlying mechanisms of glycan synthesis at the Golgi apparatus, which are still poorly understood. Important factors that determine the glycosylation potential of the Golgi apparatus are the levels and intra-Golgi localization of the glycosylation enzymes. These factors are regulated by the process of cisternal maturation which transports the cargoes through the Golgi apparatus while retaining the glycosylation enzymes in the organelle. This mechanism has till now been considered a single, house-keeping and constitutive function. Instead, we here propose that it is a mosaic of pathways, each controlling specific set of functionally related glycosylation enzymes. This changes the conception of cisternal maturation from a constitutive to a highly regulated function. In this new light, we discuss potential new groups oncogenes among the cisternal maturation machinery that can contribute to aberrant glycosylation observed in cancer cells. Further, we also discuss the prospects of novel anticancer treatments targeting the intra-Golgi trafficking process, particularly the cisternal maturation mechanism, to control/inhibit the production of pro-tumorigenic glycans.

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“…They are expressed in membrane-related organelles and vesicles (e.g. endosomes, nuclei, mitochondria, and Golgi apparatus) in various eukaryotic organisms such as yeast, fruit flies, mice, and humans [4]. To date, scientists have identified more than 60 Rab proteins in humans, which have been shown to play regulatory roles in vesicle transport, protein transport, membrane localization, and fusion [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of the value of RAB family genes in prognosis of breast invasive carcinoma

et al. 2020

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Purpose: Several RAB family genes have been studied extensively and proven to play pivotal roles in the occurrence and development of certain cancers. Here, we explored commonly expressed RAB family genes in humans and their prognostic significance using bioinformatics, and then identified potential biomarkers of breast invasive carcinoma (BRCA). Materials and methods: The prognostic values (overall survival) of RAB family genes in BRCA were obtained using Gene Expression Profiling Interactive Analysis (GEPIA). The expression patterns of RAB family genes and their relationships with clinicopathological parameters in BRCA were measured using the ONCOMINE and UALCAN databases, respectively. Genetic mutations and survival analysis were investigated using the cBio Cancer Genomics Portal (c-BioPortal). Interacting genes of potential biomarkers were identified using STRING, and functional enrichment analyses were performed using FunRich v3.1.3. Results: In total, 64 RAB genes were identified and analyzed in our study. Results showed that RAB1B, RAB2A, and RAB18 were up-regulated and significantly associated with poor overall survival in BRCA. Furthermore, their higher expression was positively correlated with clinicopathological parameters (e.g. cancer stage and nodal metastasis status). DNA copy number amplifications and mRNA up-regulation were the main genetic mutations, and the altered group showed significantly poorer overall survival compared with the unaltered group. Functional enrichment analysis of RAB1B, RAB2A, and RAB18 indicated they were closely involved in GTPase activity. Conclusions:RAB1B, RAB2A, and RAB18 were up-regulated and significantly correlated with poor prognosis in BRCA. Thus, they could be applied as novel biomarkers of BRCA in future studies.

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Multiple Roles of Rab GTPases at the Golgi

Cited by 8 publications

References 214 publications

Noncanonical Rab9a action supports endosomal exit of human papillomavirus during virus entry

Noncanonical Rab9a action supports endosomal exit of human papillomavirus during virus entry

Role of the Mosaic Cisternal Maturation Machinery in Glycan Synthesis and Oncogenesis

Comprehensive analysis of the value of RAB family genes in prognosis of breast invasive carcinoma

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