Sit4p/PP6 regulates ER-to-Golgi traffic by controlling the dephosphorylation of COPII coat subunits

Bhandari, Deepali; Zhang, Jinzhong; Menon, Shekar; Lord, Christopher L.; Chen, Shuliang; Helm, Jared R.; Thorsen, Kevin; Corbett, K.D.; Hay, Jesse; Ferro‐Novick, Susan

doi:10.1091/mbc.e13-02-0114

Cited by 46 publications

(56 citation statements)

References 35 publications

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“…PP6 regulates the activities of many host proteins (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), and it is therefore possible that PP6 silencing perturbs the virus life cycle by affecting other cellular processes. However, the fact that PP6 interacts directly with the viral RdRP suggests that it plays a direct role in the viral life cycle by regulating the posttranslational modifications of viral proteins.…”

Section: Discussionmentioning

confidence: 99%

“…PP6 is a member of the PP2A subfamily of protein phosphatases, cellular enzymes that catalyze the liberation of inorganic phosphate from proteins and peptides at serine or threonine residues (22). PP6 is a significant regulator of a number of cellular processes, including chromosome stability and the DNA damage response (23)(24)(25)(26)(27), mitosis and the regulation of cell cycle progression (22,(28)(29)(30)(31), signaling (32,33), pre-mRNA splicing (34), and vesicular trafficking (35). The catalytic subunit PPP6C and the regulatory subunits PPP6R1 and PPP6R3 were found to copurify with the viral RdRP.…”

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confidence: 99%

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Interactome Analysis of the Influenza A Virus Transcription/Replication Machinery Identifies Protein Phosphatase 6 as a Cellular Factor Required for Efficient Virus Replication

York

Hutchinson

Fodor

2014

J Virol

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The negative-sense RNA genome of influenza A virus is transcribed and replicated by the viral RNA-dependent RNA polymerase (RdRP). The viral RdRP is an important host range determinant, indicating that its function is affected by interactions with cellular factors. However, the identities and the roles of most of these factors remain unknown. Here, we employed affinity purification followed by mass spectrometry to identify cellular proteins that interact with the influenza A virus RdRP in infected human cells. We purified RdRPs using a recombinant influenza virus in which the PB2 subunit of the RdRP is fused to a Strep-tag. When this tagged subunit was purified from infected cells, copurifying proteins included the other RdRP subunits (PB1 and PA) and the viral nucleoprotein and neuraminidase, as well as 171 cellular proteins. Label-free quantitative mass spectrometry revealed that the most abundant of these host proteins were chaperones, cytoskeletal proteins, importins, proteins involved in ubiquitination, kinases and phosphatases, and mitochondrial and ribosomal proteins. Among the phosphatases, we identified three subunits of the cellular serine/threonine protein phosphatase 6 (PP6), including the catalytic subunit PPP6C and regulatory subunits PPP6R1 and PPP6R3. PP6 was found to interact directly with the PB1 and PB2 subunits of the viral RdRP, and small interfering RNA ( Viruses are obligate intracellular parasites that have been compelled by evolutionary processes to encode a minimal number of proteins for the completion of an infectious life cycle, in order to infect naive hosts and to persist in nature. This is exemplified by RNA viruses, the genomes of which are generally smaller than the genomes of DNA viruses, and therefore they greatly rely on the exploitation and subversion of host cellular proteins, structures, and pathways to facilitate virus replication (1). Transcription and replication of the influenza A virus genome are performed by the virally encoded RNA-dependent RNA polymerase (RdRP), a major determinant of species tropism and pathogenicity and a key player in the adaptation of avian influenza A viruses to mammalian hosts. These characteristics of the viral RdRP are thought to be governed by numerous interactions with cellular factors (reviewed in references 2 and 3). It is therefore of great importance to understand the relationship between the viral transcription/replication machinery and host cellular factors in order to understand how the host cell can influence the function of the viral transcription/replication machinery and vice versa. Insight into the molecular biology of these relationships could lead to novel antiviral strategies and has the potential to identify host-specific interactions that would act as a barrier to pandemic emergence.The genome of influenza A virus, like that of other members of the Orthomyxoviridae, is segmented and consists of eight individual viral ribonucleoprotein (vRNP) complexes. Each vRNP contains single-stranded viral RNA (vRNA) that is en...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Interactome Analysis of the Influenza A Virus Transcription/Replication Machinery Identifies Protein Phosphatase 6 as a Cellular Factor Required for Efficient Virus Replication

York

Hutchinson

Fodor

2014

J Virol

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“…The Golgi-localized protein kinase CK1δ (Lord et al 2011) and the protein phosphatase PP6 (Bhandari et al 2013) both act on Sec23–Sec24 (Fig. 3Ci).…”

Section: Post-translational Modification Of Copiimentioning

confidence: 99%

COPII-dependent ER export in animal cells: adaptation and control for diverse cargo

McCaughey

Stephens

2018

Histochem Cell Biol

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The export of newly synthesized proteins from the endoplasmic reticulum is fundamental to the ongoing maintenance of cell and tissue structure and function. After co-translational translocation into the ER, proteins destined for downstream intracellular compartments or secretion from the cell are sorted and packaged into transport vesicles by the COPII coat protein complex. The fundamental discovery and characterization of the pathway has now been augmented by a greater understanding of the role of COPII in diverse aspects of cell function. We now have a deep understanding of how COPII contributes to the trafficking of diverse cargoes including extracellular matrix molecules, developmental signalling proteins, and key metabolic factors such as lipoproteins. Structural and functional studies have shown that the COPII coat is both highly flexible and subject to multiple modes of regulation. This has led to new discoveries defining roles of COPII in development, autophagy, and tissue organization. Many of these newly emerging features of the canonical COPII pathway are placed in a context of procollagen secretion because of the fundamental interest in how a coat complex that typically generates 80-nm transport vesicles can package a cargo reported to be over 300 nm. Here we review the current understanding of COPII and assess the current consensus on its role in packaging diverse cargo proteins.

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“…If multiple COPII vesicles are all tethered to the same membrane structure, these vesicles will naturally cluster. Some of the tethering events may be controlled by cycles of phosphorylation and dephosphorylation of COPII coat subunits [42 •]. Studies of Golgi stack formation suggest that tethering proteins help to nucleate cisternal assembly [43, 44].…”

Section: To the Golgi: The Cisternal Assembly Stagementioning

confidence: 99%

Golgi compartmentation and identity

Papanikou

Glick

2014

Current Opinion in Cell Biology

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Recent work supports the idea that cisternae of the Golgi apparatus can be assigned to three classes, which correspond to discrete stages of cisternal maturation. Each stage has a unique pattern of membrane traffic. At the first stage, cisternae form in association with the ER at multifunctional membrane assembly stations. At the second stage, cisternae synthesize carbohydrates while exchanging material via COPI vesicles. At the third stage, cisternae of the trans-Golgi network segregate into domains and produce transport carriers with the aid of specific lipids and the actin cytoskeleton. These processes are coordinated by cascades of Rab and Arf/Arl GTPases.

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Sit4p/PP6 regulates ER-to-Golgi traffic by controlling the dephosphorylation of COPII coat subunits

Cited by 46 publications

References 35 publications

Interactome Analysis of the Influenza A Virus Transcription/Replication Machinery Identifies Protein Phosphatase 6 as a Cellular Factor Required for Efficient Virus Replication

Interactome Analysis of the Influenza A Virus Transcription/Replication Machinery Identifies Protein Phosphatase 6 as a Cellular Factor Required for Efficient Virus Replication

COPII-dependent ER export in animal cells: adaptation and control for diverse cargo

Golgi compartmentation and identity

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