A role for Rab30 in retrograde trafficking and maintenance of endosome-TGN organization

Zulkefli, Khalisah Liyana; Mahmoud, Ismail Sami; Williamson, Nicholas A.; Gosavi, Prajakta; Houghton, Fiona; Gleeson, Paul

doi:10.1016/j.yexcr.2020.112442

Cited by 10 publications

(10 citation statements)

References 46 publications

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“…Additionally, ARF1 and ARF4 double KD also resulted in tubulation of REs and inhibited retrograde endosome-to-TGN transport (Nakai et al, 2013), without affecting endocytic recycling (Volpicelli-Daley et al, 2005;Nakai et al, 2013). ARF4 has been recently identified as an interactor of active GTP-bound Rab30, which also plays a role in the same recycling pathway (Zulkefli et al, 2021). Taken together, ARF1 may differentially regulate export from REs to either the PM (together with ARF3) or the TGN (with ARF4).…”

Section: The Role Of Arfs In Trafficking In the Endo-lysosomal Systemmentioning

confidence: 93%

ARF GTPases and Their Ubiquitous Role in Intracellular Trafficking Beyond the Golgi

Adarska

Wong-Dilworth

Bottanelli

2021

Front. Cell Dev. Biol.

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Molecular switches of the ADP-ribosylation factor (ARF) GTPase family coordinate intracellular trafficking at all sorting stations along the secretory pathway, from the ER-Golgi-intermediate compartment (ERGIC) to the plasma membrane (PM). Their GDP-GTP switch is essential to trigger numerous processes, including membrane deformation, cargo sorting and recruitment of downstream coat proteins and effectors, such as lipid modifying enzymes. While ARFs (in particular ARF1) had mainly been studied in the context of coat protein recruitment at the Golgi, COPI/clathrin-independent roles have emerged in the last decade. Here we review the roles of human ARF1-5 GTPases in cellular trafficking with a particular emphasis on their roles in post-Golgi secretory trafficking and in sorting in the endo-lysosomal system.

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Section: The Role Of Arfs In Trafficking In the Endo-lysosomal Systemmentioning

confidence: 93%

ARF GTPases and Their Ubiquitous Role in Intracellular Trafficking Beyond the Golgi

Adarska

Wong-Dilworth

Bottanelli

2021

Front. Cell Dev. Biol.

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“…However, BFA leads to reduced staining intensity of cis -/medial Golgi proteins, while it was increased in Vti1a/b DKO and no TGN tubulation was observed. Rab30 deficiency also causes dispersal of TGN proteins, but causes only a mild perturbation of cis -Golgi protein GM130 29 . Furthermore, ARL1 is important for maintenance of Golgi morphology 30 .…”

Section: Discussionmentioning

confidence: 99%

Vti1a/b support distinct aspects of TGN and cis-/medial Golgi organization

Bommel

Toonen

Verhage

2022

Sci Rep

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Retrograde trafficking towards the trans-Golgi network (TGN) is important for dense core vesicle (DCV) biogenesis. Here, we used Vti1a/b deficient neurons to study the impact of disturbed retrograde trafficking on Golgi organization and cargo sorting. In Vti1a/b deficient neurons, staining intensity of cis-/medial Golgi proteins (e.g., GM130 and giantin) was increased, while the intensity of two recycling TGN proteins, TGN38 and TMEM87A, was decreased and the TGN-resident protein Golgin97 was normal. Levels and localization of DCV cargo markers, LAMP1 and KDEL were also altered. This phenotype was not caused by reduced Golgi size or absence of a TGN compartment. The phenotype was partially phenocopied by disturbing sphingolipid homeostasis, but was not rescued by overexpression of sphingomyelin synthases or the sphingolipid synthesis inhibitor myriocin. We conclude that Vti1a/b are important for distinct aspects of TGN and cis-/medial Golgi organization. Our data underline the importance of retrograde trafficking for Golgi organization, DCV cargo sorting and the distribution of proteins of the regulated secretory pathway.

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“…By recruiting different effector proteins, Arfs control the transport through the entire endosomal system and the TGN [ 14 , 17 , 24 , 25 , 67 , 78 , 79 ], whose membrane elements form the inner part of the pre-AC and the AC in the later stages of infection [ 6 , 7 , 9 , 10 ]. Arfs are also important for maintaining the structure and function of the Golgi apparatus [ 11 , 27 , 68 , 71 , 78 , 80 ], whose stacks form the outer pre-AC but retain their basic functions, such as the loading and processing of the MCMV-encoded nonstructural protein m06 and the viral glycoproteins in the late phase of infection [ 6 , 7 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

Arf GTPases Are Required for the Establishment of the Pre-Assembly Compartment in the Early Phase of Cytomegalovirus Infection

Pavišić

Lučin

Zagorac

et al. 2021

Life

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Shortly after entering the cells, cytomegaloviruses (CMVs) initiate massive reorganization of cellular endocytic and secretory pathways, which results in the forming of the cytoplasmic virion assembly compartment (AC). We have previously shown that the formation of AC in murine CMV- (MCMV) infected cells begins in the early phase of infection (at 4–6 hpi) with the pre-AC establishment. Pre-AC comprises membranes derived from the endosomal recycling compartment, early endosomes, and the trans-Golgi network, which is surrounded by fragmented Golgi cisterns. To explore the importance of Arf GTPases in the biogenesis of the pre-AC, we infected Balb 3T3 cells with MCMV and analyzed the expression and intracellular localization of Arf proteins in the early phases (up to 16 hpi) of infection and the development of pre-AC in cells with a knockdown of Arf protein expression by small interfering RNAs (siRNAs). Herein, we show that even in the early phase, MCMVs cause massive reorganization of the Arf system of the host cells and induce the over-recruitment of Arf proteins onto the membranes of pre-AC. Knockdown of Arf1, Arf3, Arf4, or Arf6 impaired the establishment of pre-AC. However, the knockdown of Arf1 and Arf6 also abolished the establishment of infection. Our study demonstrates that Arf GTPases are required for different steps of early cytomegalovirus infection, including the establishment of the pre-AC.

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A role for Rab30 in retrograde trafficking and maintenance of endosome-TGN organization

Cited by 10 publications

References 46 publications

ARF GTPases and Their Ubiquitous Role in Intracellular Trafficking Beyond the Golgi

ARF GTPases and Their Ubiquitous Role in Intracellular Trafficking Beyond the Golgi

Vti1a/b support distinct aspects of TGN and cis-/medial Golgi organization

Arf GTPases Are Required for the Establishment of the Pre-Assembly Compartment in the Early Phase of Cytomegalovirus Infection

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