Shr3p Mediates Specific COPII Coatomer–Cargo Interactions Required for the Packaging of Amino Acid Permeases Into ER-derived Transport Vesicles

Gilstring, C. Fredrik; Melin-Larsson, Monika; Ljungdahl, Per O.

doi:10.1091/mbc.10.11.3549

Cited by 64 publications

(83 citation statements)

References 79 publications

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“…3A). We also chose to duplicate SHR3, a gene encoding a membranelocalized chaperone that is specifically required for the exit of Ssy1p from the endoplasmic reticulum (21,29). By making our starting strain merodiploid for these genes, our aim was to eliminate the reisolation of recessive loss-of-function mutations in previously identified SPS sensor components.…”

Section: Resultsmentioning

confidence: 99%

The N-Terminal Regulatory Domain of Stp1p Is Modular and, Fused to an Artificial Transcription Factor, Confers Full Ssy1p-Ptr3p-Ssy5p Sensor Control

Andréasson

Ljungdahl

2004

Molecular and Cellular Biology

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Stp1p and Stp2p are homologous and redundant transcription factors that are synthesized as latent cytoplasmic proteins with N-terminal regulatory domains. In response to extracellular amino acids, the plasma membrane-localized Ssy1p-Ptr3p-Ssy5p (SPS) sensor induces an endoproteolytic processing event that cleaves away the N-terminal regulatory domains. The shorter forms of Stp1p and Stp2p are targeted to the nucleus, where they bind and activate the transcription of amino acid permease genes. A novel genetic screen, specifically designed to search for rare mutations that affect the SPS-sensing pathway, identified the F-box protein Grr1p as an obligatory factor required for Stp1p/Stp2p processing. Additionally, we have found that a null mutation in the ASI1 (amino acid sensor-independent) gene enables full-length unprocessed Stp1p/Stp2p to enter the nucleus and derepress SPS sensor-dependent genes. The N-terminal domains of Stp1p/Stp2p contain two conserved motifs that are required for proper nuclear exclusion and proteolytic processing. These motifs function in parallel; mutations that abolish processing inhibit signaling, whereas mutations that interfere with cytoplasmic retention result in constitutive derepression of SPS sensor-regulated genes independently of processing. The N-terminal domain of Stp1p is functionally autonomous and transferable to other transcription factors, where its presence confers ASI1-dependent nuclear exclusion and SPS sensor-induced proteolytic processing.All cells have the capacity to sense and respond to extracellular environmental cues by changing patterns of gene expression. Eukaryotic cells can regulate patterns of gene expression simply by controlling the movement of transcription factors across the nuclear envelope. For example, cells can synthesize transcription factors as latent forms that are excluded from entering the nucleus and, in response to discrete environmental cues, activate processes that induce their nuclear targeting. Several latent transcription factors that transfer regulatory information from the plasma membrane to the nucleus in metazoan cells have been described (9). Regulated latent transcription factors involved in signal transduction include the well-studied NF-B/Relish, Cubitus interruptus, and Notch proteins (4,5,20). In such instances, nuclear targeting not only is used to provide signals necessary for the correct timing of gene regulation but also provides the means to physically transfer signals from nonnuclear compartments to specific promoter sequences.Fundamental to understanding regulated latent transcription factors is the elucidation of the mechanisms that direct these proteins to change compartments in a controlled fashion. This change may be achieved through a protein modification that regulates the activity of intrinsic nuclear localization determinants; nuclear localization sequences (NLS) are sequence motifs recognized by the nuclear import machinery and, in the opposing manner, nuclear export sequences (NES) are sequence motifs that medi...

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Section: Resultsmentioning

confidence: 99%

The N-Terminal Regulatory Domain of Stp1p Is Modular and, Fused to an Artificial Transcription Factor, Confers Full Ssy1p-Ptr3p-Ssy5p Sensor Control

Andréasson

Ljungdahl

2004

Molecular and Cellular Biology

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“…The membrane topology of Pmt1p (18) and Shr3p (29) were determined previously, thus we used these proteins as controls. Pmt1p has been determined to have the C terminus in the lumen of the ER, whereas the C terminus of Shr3p has been shown to be in the cytosol.…”

Section: Resultsmentioning

confidence: 99%

Determination of the membrane topology of Ost4p and its subunit interactions in the oligosaccharyltransferase complex in Saccharomyces cerevisiae

Kim

Heijne

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Ost4p is a minimembrane protein containing only 36 amino acids and is a subunit of oligosaccharyltransferase (OT) in Saccharomyces cerevisiae. It was found previously when amino acid residues 18 -25 of Ost4p were mutated to ionizable amino acids and defects were observed in the interaction between Ost4p and either Stt3p or Ost3p, two other components of OT. The transmembrane segment of Ost4p is likely to extend from residues 10 -25. This is consistent with the finding that ␣-helicity is estimated to be 36% by CD analysis of synthetic Ost4p in liposomes. This value is in reasonable agreement with the assumption that amino acids 10 -25 (16 of 36 or 44%) are transmembrane. Therefore, the mutation-sensitive region (residues 18 -25) is localized to only one half of the putative transmembrane domain of Ost4p. To learn where this region of Ost4p is situated in relation to the faces of endoplasmic reticulum (ER) membrane, we determined the membrane topology of Ost4p using an in vivo method and established that it is an N lumen-Ccyto, type I membrane protein. These results indicate that the mutation-sensitive region of Ost4p is localized in the cytoplasmic leaflet of the ER membrane. In the current study, we also observed a loss of direct interaction between Ost3p and Stt3p in the presence of ost4 temperature-sensitive mutants, which indicates Ost4p, via interactions with amino acid residues in the cytosolic leaflet of the ER membrane, functions to bind these two proteins together in a subcomplex of OT.

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“…No sequence similarity can be detected between these two proteins, and whereas PHO86 has four predicted transmembrane domains, PHF1 has only one. In yeast, known accessory proteins such as GSF2, SHR3, and ERV14, which are involved in the ER exit of specific hexose transporters, specific amino acid permeases, and a membrane glycoprotein, respectively, display strikingly different structures (Gilstring et al, 1999;Sherwood and Carlson, 1999;Powers and Barlowe, 2002). The fact that PHF1 and PHO86 both act on closely related proteins (Pi transporters) strongly suggests that the existence of structural diversity among accessory proteins reflects fairly loose structural constraints for performing this type of function.…”

Section: Discussionmentioning

confidence: 99%

PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 Is a Plant-Specific SEC12-Related Protein That Enables the Endoplasmic Reticulum Exit of a High-Affinity Phosphate Transporter in Arabidopsis [W]

et al. 2005

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PHOSPHATE TRANSPORTER1 (PHT1) genes encode phosphate (Pi) transporters that play a fundamental role in Pi acquisition and remobilization in plants. Mutation of the Arabidopsis thaliana PHOSPHATE TRANSPORTER TRAFFIC FACILITA-TOR1 (PHF1) impairs Pi transport, resulting in the constitutive expression of many Pi starvation-induced genes, increased arsenate resistance, and reduced Pi accumulation. PHF1 expression was detected in all tissues, particularly in roots, flowers, and senescing leaves, and was induced by Pi starvation, thus mimicking the expression patterns of the whole PHT1 gene family. PHF1 was localized in endoplasmic reticulum (ER), and mutation of PHF1 resulted in ER retention and reduced accumulation of the plasma membrane PHT1;1 transporter. By contrast, the PIP2A plasma membrane protein was not mislocalized, and the secretion of Pi starvation-induced RNases was not affected in the mutant. PHF1 encodes a plantspecific protein structurally related to the SEC12 proteins of the early secretory pathway. However, PHF1 lacks most of the conserved residues in SEC12 proteins essential as guanine nucleotide exchange factors. Although it functions in early secretory trafficking, PHF1 likely evolved a novel mechanism accompanying functional specialization on Pi transporters. The identification of PHF1 reveals that plants are also endowed with accessory proteins specific for selected plasma membrane proteins, allowing their exit from the ER, and that these ER exit cofactors may have a phylum-specific origin.

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Shr3p Mediates Specific COPII Coatomer–Cargo Interactions Required for the Packaging of Amino Acid Permeases Into ER-derived Transport Vesicles

Cited by 64 publications

References 79 publications

The N-Terminal Regulatory Domain of Stp1p Is Modular and, Fused to an Artificial Transcription Factor, Confers Full Ssy1p-Ptr3p-Ssy5p Sensor Control

The N-Terminal Regulatory Domain of Stp1p Is Modular and, Fused to an Artificial Transcription Factor, Confers Full Ssy1p-Ptr3p-Ssy5p Sensor Control

Determination of the membrane topology of Ost4p and its subunit interactions in the oligosaccharyltransferase complex in Saccharomyces cerevisiae

PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 Is a Plant-Specific SEC12-Related Protein That Enables the Endoplasmic Reticulum Exit of a High-Affinity Phosphate Transporter in Arabidopsis [W]

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