Interorganelle communication and membrane shaping in the early secretory pathway

Luján, Pablo; Angulo-Capel, Jessica; Chabanon, Morgan; Campelo, Felix

doi:10.1016/j.ceb.2021.01.010

Cited by 24 publications

(21 citation statements)

References 80 publications

(111 reference statements)

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“…[16,22] The conventional secretory pathway controls the exocytosis of a large number of proinflammatory cytokines and chemokines and the surface expression of transmembrane receptors. [56][57][58][59][60] Interestingly, however, we found that neither TNF-nor IL-1𝛽induced secretion of CXCL1 or IL-6 was affected by knockout of RNF115. In addition, the cell surface expression of MHC-I and the integrin molecules such as CD11b or CD11c which is mediated by the conventional secretory pathway was comparable between Rnf115 +/+ and Rnf115 −/− BMDCs.…”

Section: Discussionmentioning

confidence: 99%

RNF115 Inhibits the Post‐ER Trafficking of TLRs and TLRs‐Mediated Immune Responses by Catalyzing K11‐Linked Ubiquitination of RAB1A and RAB13

Zhang

Gan

et al. 2022

Advanced Science

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The subcellular localization and intracellular trafficking of Toll-like receptors (TLRs) critically regulate TLRs-mediated antimicrobial immunity and autoimmunity. Here, it is demonstrated that the E3 ubiquitin ligase RNF115 inhibits the post-endoplasmic reticulum (ER) trafficking of TLRs and TLRs-mediated immune responses by catalyzing ubiquitination of the small GTPases RAB1A and RAB13. It is shown that the 14-3-3 chaperones bind to AKT1-phosphorylated RNF115 and facilitate RNF115 localizing on the ER and the Golgi apparatus. RNF115 interacts with RAB1A and RAB13 and catalyzes K11-linked ubiquitination on the Lys49 and Lys61 residues of RAB1A and on the Lys46 and Lys58 residues of RAB13, respectively. Such a modification impairs the recruitment of guanosine diphosphate (GDP) dissociation inhibitor 1 (GDI1) to RAB1A and RAB13, a prerequisite for the reactivation of RAB proteins. Consistently, knockdown of RAB1A and RAB13 in Rnf115 +/+ and Rnf115 −/− cells markedly inhibits the post-ER and the post-Golgi trafficking of TLRs, respectively. In addition, reconstitution of RAB1A K49/61R or RAB13 K46/58R into Rnf115 +/+ cells but not Rnf115 −/− cells promotes the trafficking of TLRs from the ER to the Golgi apparatus and from the Golgi apparatus to the cell surface, respectively. These findings uncover a common and step-wise regulatory mechanism for the post-ER trafficking of TLRs.

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Section: Discussionmentioning

confidence: 99%

RNF115 Inhibits the Post‐ER Trafficking of TLRs and TLRs‐Mediated Immune Responses by Catalyzing K11‐Linked Ubiquitination of RAB1A and RAB13

Zhang

Gan

et al. 2022

Advanced Science

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“…Interestingly, super-resolution nanoscopy showed that CARTS seem to form in TGN regions that are separate but adjacent to ER-Golgi MCSs [ 41 ]. How ER-Golgi MCSs mechanistically mediate CARTS biogenesis still remains to be fully elucidated [ 118 ], but there is experimental evidence that suggests a prominent role for lipids in this process.…”

Section: Lipid Requirements For Pkd-mediated Carts Formationmentioning

confidence: 99%

“…ER-Golgi MCSs have been identified as platforms for the fast and directional transport of lipids between these two organelles, and hence emerge as key organizers of lipid homeostasis in the secretory pathway [ 118 , 119 , 120 ] ( Figure 3 ). These contact sites are established by the ER-localized VAP proteins.…”

Section: Lipid Requirements For Pkd-mediated Carts Formationmentioning

confidence: 99%

“…We have also reviewed a number of upstream activators of PKD ( Section 2 ). However, a key question in the field that still remains open is how membrane trafficking is regulated in response to physiological needs [ 3 , 4 , 5 , 118 , 147 ]. We discuss here different signaling pathways that transduce cellular cues into signals to control the secretory flow.…”

Section: Signaling At the Golgi Membranes For The Regulation Of Protein Secretionmentioning

confidence: 99%

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The PKD-Dependent Biogenesis of TGN-to-Plasma Membrane Transport Carriers

Wakana

Campelo

2021

Cells

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Membrane trafficking is essential for processing and transport of proteins and lipids and to establish cell compartmentation and tissue organization. Cells respond to their needs and control the quantity and quality of protein secretion accordingly. In this review, we focus on a particular membrane trafficking route from the trans-Golgi network (TGN) to the cell surface: protein kinase D (PKD)-dependent pathway for constitutive secretion mediated by carriers of the TGN to the cell surface (CARTS). Recent findings highlight the importance of lipid signaling by organelle membrane contact sites (MCSs) in this pathway. Finally, we discuss our current understanding of multiple signaling pathways for membrane trafficking regulation mediated by PKD, G protein-coupled receptors (GPCRs), growth factors, metabolites, and mechanosensors.

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“…TGN46 exits the TGN in specific carriers called CARTS (carriers of the TGN to the cell surface). Protein kinase D (PKD), known for its role in events leading to the fission of cargo-containing carriers at the TGN, is required for the production of CARTS 2,[33][34][35] . How secretory cargoes are sorted and specifically packed into CARTS is not known.…”

Section: Introductionmentioning

confidence: 99%

Sorting of secretory proteins at the trans-Golgi network by human TGN46

Luján

Garcia‐Cabau

Wakana

et al. 2022

Preprint

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Secretory proteins are sorted at the trans-Golgi network (TGN) for export into specific transport carriers. However, the molecular players involved in this fundamental process remain largely elusive. Here, we identified the transmembrane protein TGN46 as a cargo receptor for the export of secretory proteins in CARTS – a class of protein kinase D-dependent TGN-to-plasma membrane carriers. We show that TGN46 is necessary for cargo sorting and loading into nascent carriers at the TGN. By combining quantitative fluorescence microscopy and mutagenesis approaches, we further discovered that the TGN46 lumenal domain encodes for its cargo sorting function. Interestingly, this domain forms liquid droplets in vitro by means of liquid-liquid phase separation, a physical mechanism that may assist in TGN46-mediated cargo sorting. In summary, our results define a cellular function of TGN46 in sorting secretory proteins for export from the TGN. These findings could open new therapeutic avenues for diseases that parallel secretory malfunction.

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Interorganelle communication and membrane shaping in the early secretory pathway

Cited by 24 publications

References 80 publications

RNF115 Inhibits the Post‐ER Trafficking of TLRs and TLRs‐Mediated Immune Responses by Catalyzing K11‐Linked Ubiquitination of RAB1A and RAB13

RNF115 Inhibits the Post‐ER Trafficking of TLRs and TLRs‐Mediated Immune Responses by Catalyzing K11‐Linked Ubiquitination of RAB1A and RAB13

The PKD-Dependent Biogenesis of TGN-to-Plasma Membrane Transport Carriers

Sorting of secretory proteins at the trans-Golgi network by human TGN46

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