Serine-ubiquitination regulates Golgi morphology and the secretory pathway upon Legionella infection

AbstractSidE family of Legionella effectors catalyze non-canonical phosphoribosyl-linked ubiquitination (PR-ubiquitination) of host proteins during bacterial infection. SdeA localizes predominantly to ER and partially to the Golgi apparatus, and mediates serine ubiquitination of multiple ER and Golgi proteins. Here we show that SdeA causes disruption of Golgi integrity due to its ubiquitin ligase activity. The Golgi linking proteins GRASP55 and GRASP65 are PR-ubiquitinated on multiple serine residues, thus preventing their ability to cluster and form oligomeric structures. In addition, we found that the functional consequence of Golgi disruption is not linked to the recruitment of Golgi membranes to the growing Legionella-containing vacuoles. Instead, it affects the host secretory pathway. Taken together, our study sheds light on the Golgi manipulation strategy by which Legionella hijacks the secretory pathway and promotes bacterial infection.

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Serine-ubiquitination regulates Golgi morphology and the secretory pathway upon Legionella infection

10.1101/2020.07.27.223842 ◽

2020 ◽

Author(s):

Yaobin Liu ◽

Rukmini Mukherjee ◽

Florian Bonn ◽

Thomas Colby ◽

Ivan Matic ◽

...

Keyword(s):

Golgi Apparatus ◽

Bacterial Infection ◽

Ubiquitin Ligase ◽

Secretory Pathway ◽

Cytokine Release ◽

Host Proteins ◽

Functional Consequence ◽

Golgi Membranes ◽

Ubiquitin Ligase Activity ◽

Manipulation Strategy

AbstractSidE family of Legionella effectors catalyze non-canonical phosphoribosyl-linked ubiquitination (PR-ubiquitination) of host proteins during bacterial infection. SdeA localizes predominantly to ER and partially to the Golgi apparatus, and mediates serine ubiquitination of multiple ER and Golgi proteins. Here we show that SdeA causes disruption of Golgi integrity due to its ubiquitin ligase activity. The Golgi linking proteins GRASP55 and GRASP65 are PR-ubiquitinated on multiple serine residues, thus preventing their ability to cluster and form oligomeric structures. In addition, we found that the functional consequence of Golgi disruption is not linked to the recruitment of Golgi membranes to the growing Legionella-containing vacuoles. Instead, it affects the secretory pathway, including cytokine release in cells. Taken together, our study sheds light on the Golgi manipulation strategy by which Legionella hijacks the secretory pathway and promotes bacterial infection.

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The transmembrane protein p23 contributes to the organization of the Golgi apparatus

Journal of Cell Science ◽

10.1242/jcs.113.6.1043 ◽

2000 ◽

Vol 113 (6) ◽

pp. 1043-1057 ◽

Cited By ~ 2

Author(s):

M. Rojo ◽

G. Emery ◽

V. Marjomaki ◽

A.W. McDowall ◽

R.G. Parton ◽

...

Keyword(s):

Golgi Apparatus ◽

Secretory Pathway ◽

Transmembrane Protein ◽

Ectopic Expression ◽

Retrograde Transport ◽

Early Secretory Pathway ◽

Golgi Membranes ◽

Constant Diameter ◽

Golgi Network

In previous studies we have shown that p23, a member of the p24-family of small transmembrane proteins, is highly abundant in membranes of the cis-Golgi network (CGN), and is involved in sorting/trafficking in the early secretory pathway. In the present study, we have further investigated the role of p23 after ectopic expression. We found that ectopically expressed p23 folded and oligomerized properly, even after overexpression. However, in contrast to endogenous p23, exogenous p23 molecules did not localize to the CGN, but induced a significant expansion of characteristic smooth ER membranes, where they accumulated in high amounts. This ER-derived, p23-rich subdomain displayed a highly regular morphology, consisting of tubules and/or cisternae of constant diameter, which were reminiscent of the CGN membranes containing p23 in control cells. The expression of exogenous p23 also led to the specific relocalization of endogenous p23, but not of other proteins, to these specialized ER-derived membranes. Relocalization of p23 modified the ultrastructure of the CGN and Golgi membranes, but did not affect anterograde and retrograde transport reactions to any significant extent. We conclude (i) that p23 has a morphogenic activity that contributes to the morphology of CGN-membranes; and (ii) that the presence of p23 in the CGN is necessary for the proper organization of the Golgi apparatus.

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A zebrafish (Danio rerio) bloodthirsty member 20 with E3 ubiquitin ligase activity involved in immune response against bacterial infection

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2014.12.081 ◽

2015 ◽

Vol 457 (1) ◽

pp. 83-89 ◽

Cited By ~ 11

Author(s):

Xinshang Zhang ◽

Heng Zhao ◽

Yeyu Chen ◽

Huiying Luo ◽

Peilong Yang ◽

...

Keyword(s):

Immune Response ◽

Bacterial Infection ◽

Ubiquitin Ligase ◽

Danio Rerio ◽

E3 Ubiquitin Ligase ◽

Ubiquitin Ligase Activity

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Faculty Opinions recommendation of The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1013426.192151 ◽

2003 ◽

Author(s):

Antony Carr

Keyword(s):

Dna Damage ◽

Ubiquitin Ligase ◽

Cop9 Signalosome ◽

Ubiquitin Ligase Activity

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Faculty Opinions recommendation of The E3 ubiquitin ligase activity of RING1B is not essential for early mouse development.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725799223.793526294 ◽

2016 ◽

Author(s):

Anton Wutz

Keyword(s):

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

Mouse Development ◽

Ubiquitin Ligase Activity ◽

Early Mouse

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Normal Immune System Development in Mice Lacking the Deltex-1 RING Finger Domain

Molecular and Cellular Biology ◽

10.1128/mcb.25.4.1437-1445.2005 ◽

2005 ◽

Vol 25 (4) ◽

pp. 1437-1445 ◽

Cited By ~ 15

Author(s):

Sébastien Storck ◽

Frédéric Delbos ◽

Nicolas Stadler ◽

Catherine Thirion-Delalande ◽

Florence Bernex ◽

...

Keyword(s):

B Cell ◽

Notch Signaling ◽

Ubiquitin Ligase ◽

Cell Lineage ◽

Ring Finger ◽

Mouse Development ◽

Ring Finger Domain ◽

Ubiquitin Ligase Activity ◽

Immune System Development ◽

Cell Commitment

ABSTRACT The Notch signaling pathway controls several cell fate decisions during lymphocyte development, from T-cell lineage commitment to the peripheral differentiation of B and T lymphocytes. Deltex-1 is a RING finger ubiquitin ligase which is conserved from Drosophila to humans and has been proposed to be a regulator of Notch signaling. Its pattern of lymphoid expression as well as gain-of-function experiments suggest that Deltex-1 regulates both B-cell lineage and splenic marginal-zone B-cell commitment. Deltex-1 was also found to be highly expressed in germinal-center B cells. To investigate the physiological function of Deltex-1, we generated a mouse strain lacking the Deltex-1 RING finger domain, which is essential for its ubiquitin ligase activity. Deltex-1Δ/Δ mice were viable and fertile. A detailed histological analysis did not reveal any defects in major organs. T- and B-cell development was normal, as were humoral responses against T-dependent and T-independent antigens. These data indicate that the Deltex-1 ubiquitin ligase activity is dispensable for mouse development and immune function. Possible compensatory mechanisms, in particular those from a fourth Deltex gene identified during the course of this study, are also discussed.

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