Getting membrane proteins on and off the shuttle bus between the endoplasmic reticulum and the Golgi complex

Borgese, Nica

doi:10.1242/jcs.183335

Cited by 51 publications

(57 citation statements)

References 121 publications

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“…Mobile ER-resident proteins such as calreticulin, BiP, PDI, ERp57, and calnexin are not detected in the ERES (Balch et al 1994, Mezzacasa & Helenius 2002. Certain transmembrane proteins with a single, short transmembrane domain (TMD) are also virtually excluded, although freely diffusible elsewhere in the ER membrane (Borgese 2016). Given the distribution of a mutant glycoprotein of vesicular stomatitis virus (VSV-G) and misfolded carboxypeptidase Y (CPY * ), incompletely folded cargo proteins are not only excluded but actively removed from ERES (Hsu et al 2012, Mezzacasa & Helenius 2002.…”

Section: Figurementioning

confidence: 99%

“…Certain folded proteins with a TMD shorter than 17 amino acids are excluded from the ERES, whereas proteins with a 22-amino-acid TMD are not (Dukhovny et al 2009, Ronchi et al 2008. TMD length can also determine whether membrane proteins are exported (Borgese 2016). The lipid composition and biophysical properties of the membrane in ERES may differ from the rest of the ER, and ERES may be less accepting of short TMDs.…”

Section: Is There a Retention Matrix?mentioning

confidence: 99%

“…Two consequences of collecting cargo receptors and their cargo in the ERES may be to accelerate vesicle formation and to generate a membrane microdomain with properties that allow inclusion of cargo that by itself is devoid of export signals (Borgese 2016). In other words, the cargo capture process may promote bulk flow.…”

Section: Creating Membrane Microdomains In Eres That Promote Bulk Flowmentioning

confidence: 99%

“…Where do we stand today? For some influential reviews from different periods in this ongoing debate, see Bonifacino & Glick (2004), Borgese (2016), Geva & Schuldiner (2014), Hauri et al (2000), Herrmann et al (1999), Hurtley & Helenius (1989), Hutt & Balch (2013), Lee et al (2004), Lippincott-Schwartz et al (2000), Mayor & Riezman (2004), Palade (1975), Pelham (1994), Pfeffer & Rothman (1987), Warren & Mellman (1999), and Zanetti et al (2012).…”

Section: Introductionmentioning

confidence: 99%

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Cargo Capture and Bulk Flow in the Early Secretory Pathway

Barlowe

Helenius

2016

Annu. Rev. Cell Dev. Biol.

175

191

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Transport of newly synthesized proteins from the endoplasmic reticulum (ER) to the Golgi complex is highly selective. As a general rule, such transport is limited to soluble and membrane-associated secretory proteins that have reached properly folded and assembled conformations. To secure the efficiency, fidelity, and control of this crucial transport step, cells use a combination of mechanisms. The mechanisms are based on selective retention of proteins in the ER to prevent uptake into transport vesicles, on selective capture of proteins in COPII carrier vesicles, on inclusion of proteins in these vesicles by default as part of fluid and membrane bulk flow, and on selective retrieval of proteins from post-ER compartments by retrograde vesicle transport.

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Section: Figurementioning

confidence: 99%

Section: Is There a Retention Matrix?mentioning

confidence: 99%

Section: Creating Membrane Microdomains In Eres That Promote Bulk Flowmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cargo Capture and Bulk Flow in the Early Secretory Pathway

Barlowe

Helenius

2016

Annu. Rev. Cell Dev. Biol.

175

191

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“…Therefore, the mechanisms by which membrane proteins target the plasma membrane and the cytoplasmic membranous organelles are distinct from those by which membrane proteins specifically accumulate at the NM. The membrane proteins targeted to the plasma membrane and the cytoplasmic membranous organelles are in general sorted from the ER by the vesicular trafficking system (54). In contrast, recent live-imaging and mathematical analyses support the diffusion and retention model for specific targeting of membrane proteins to the NM (55,56).…”

Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus 1 UL34 Protein Regulates the Global Architecture of the Endoplasmic Reticulum in Infected Cells

Maeda

Arii

Hirohata

et al. 2017

J Virol

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Upon herpes simplex virus 1 (HSV-1) infection, the CD98 heavy chain (CD98hc) is redistributed around the nuclear membrane (NM), where it promotes viral de-envelopment during the nuclear egress of nucleocapsids. In this study, we attempted to identify the factor(s) involved in CD98hc accumulation and demonstrated the following: (i) the null mutation of HSV-1 UL34 caused specific dispersion throughout the cytoplasm of CD98hc and the HSV-1 de-envelopment regulators, glycoproteins B and H (gB and gH); (ii) as observed with CD98hc, gB, and gH, wild-type HSV-1 infection caused redistribution of the endoplasmic reticulum (ER) markers calnexin and ERp57 around the NM, whereas the UL34-null mutation caused cytoplasmic dispersion of these markers; (iii) the ER markers colocalized efficiently with CD98hc, gB, and gH in the presence and absence of UL34 in HSV-1-infected cells; (iv) at the ultrastructural level, wild-type HSV-1 infection caused ER compression around the NM, whereas the UL34-null mutation caused cytoplasmic dispersion of the ER; and (v) the UL34-null mutation significantly decreased the colocalization efficiency of lamin protein markers of the NM with CD98hc and gB. Collectively, these results indicate that HSV-1 infection causes redistribution of the ER around the NM, with resulting accumulation of ER-associated CD98hc, gB, and gH around the NM and that UL34 is required for ER redistribution, as well as for efficient recruitment to the NM of the ER-associated de-envelopment factors. Our study suggests that HSV-1 induces remodeling of the global ER architecture for recruitment of regulators mediating viral nuclear egress to the NM. IMPORTANCEThe ER is an important cellular organelle that exists as a complex network extending throughout the cytoplasm. Although viruses often remodel the ER to facilitate viral replication, information on the effects of herpesvirus infections on ER morphological integrity is limited. Here, we showed that HSV-1 infection led to compression of the global ER architecture around the NM, resulting in accumulation of ER-associated regulators associated with nuclear egress of HSV-1 nucleocapsids. We also identified HSV-1 UL34 as a viral factor that mediated ER remodeling. Furthermore, we demonstrated that UL34 was required for efficient targeting of these regulators to the NM. To our knowledge, this is the first report showing that a herpesvirus remodels ER global architecture. Our study also provides insight into the mechanism by which the regulators for HSV-1 nuclear egress are recruited to the NM, where this viral event occurs.KEYWORDS ER, herpes simplex virus, organelle structure H erpes simplex virus 1 (HSV-1) is classified in the subfamily Alphaherpesvirinae of the family Herpesviridae. It is one of the best-studied members of the family and is an important human pathogen, causing a variety of disease states, including mucocuta-

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Disrupted ER‐to‐Golgi trafficking underlies anti‐HIV drugs and alcohol‐induced cellular stress and hepatic injury

Han

et al. 2017

Hepatology Communications

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Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti‐human immunodeficiency virus (HIV) drugs and alcohol‐induced liver disease in a significant number of patients infected with HIV. However, the precise mechanism by which the drugs and alcohol cause ER stress remains elusive. We found that ritonavir‐boosted lopinavir (RL) activated two canonical UPR branches without activation of the third canonical activating transcription factor 6 (ATF6) branch in either HepG2 cells or primary mouse hepatocytes. In the RL‐treated cells, ATF6 localization in the Golgi apparatus required for its activation was reduced; this was followed by Golgi fragmentation and dislocation/redistribution of Golgi‐resident enzymes. Severities of Golgi fragmentation induced by other anti‐HIV drugs varied and were correlated with the ER stress response. In the liver of mice fed RL, alcohol feeding deteriorated the Golgi fragmentation, which was correlated with ER stress, elevated alanine aminotransferase, and liver steatosis. The Golgi stress response (GSR) markers GCP60 and HSP47 were increased in RL‐treated liver cells, and knockdown of transcription factor for immunoglobulin heavy‐chain enhancer 3 of the GSR by small interfering RNA worsened RL‐induced cell death. Cotreatment of pharmacological agent H89 with RL inhibited the RL‐induced Golgi enzyme dislocation and ER stress. Moreover, the coat protein complex II (COPII) complexes that mediate ER‐to‐Golgi trafficking accumulated in the RL‐treated liver cells; this was not due to interference of RL with the initial assembly of the COPII complexes. RL also inhibited Golgi fragmentation and reassembly induced by short treatment and removal of brefeldin A. Conclusion: Our study indicates that ER‐to‐Golgi trafficking is disrupted by anti‐HIV drugs and/or alcohol, and this contributes to subsequent ER stress and hepatic injury. (Hepatology Communications 2017;1:122‐139)

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Getting membrane proteins on and off the shuttle bus between the endoplasmic reticulum and the Golgi complex

Cited by 51 publications

References 121 publications

Cargo Capture and Bulk Flow in the Early Secretory Pathway

Cargo Capture and Bulk Flow in the Early Secretory Pathway

Herpes Simplex Virus 1 UL34 Protein Regulates the Global Architecture of the Endoplasmic Reticulum in Infected Cells

Disrupted ER‐to‐Golgi trafficking underlies anti‐HIV drugs and alcohol‐induced cellular stress and hepatic injury

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