Brefeldin A's effects on endosomes, lysosomes, and the TGN suggest a general mechanism for regulating organelle structure and membrane traffic

Lippincott‐Schwartz, Jennifer; Yuan, Lydia C.; Tipper, Christopher; Amherdt, M; Orci, Lelio; Klausner, Richard D.

doi:10.1016/0092-8674(91)90534-6

Cited by 799 publications

(590 citation statements)

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“…This is of particular interest in the light of our previous observations concerning the effects of brefeldin A (BFA) on BG morphology and distribution (Mc Dermott et al, 2002;McDermott et al, 2004). BFA treatment, like Rab11AS25N overexpression, results in tubularization of the ERC in many cell types (Lippincott-Schwartz et al, 1991;Wilcke et al, 2000;Holtta-Vuori et al, 2002), including the cellular models used in this study (McDermott et al, 2004). However, BFA induces fusion of BGs with other compartments of the endocytic system, but it does not cause their disappearance.…”

Section: Discussionmentioning

confidence: 96%

Rab11A Controls the Biogenesis of Birbeck Granules by Regulating Langerin Recycling and Stability

Uzan-Gafsou

Bausinger²,

Proamer³

et al. 2007

MBoC

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The extent to which Rab GTPases, Rab-interacting proteins, and cargo molecules cooperate in the dynamic organization of membrane architecture remains to be clarified. Langerin, a recycling protein accumulating in the Rab11-positive compartments of Langerhans cells, induces the formation of Birbeck granules (BGs), which are membrane subdomains of the endosomal recycling network. We investigated the role of Rab11A and two members of the Rab11 family of interacting proteins, Rip11 and RCP, in Langerin traffic and the biogenesis of BGs. The overexpression of a dominant-negative Rab11A mutant or Rab11A depletion strongly influenced Langerin traffic and stability and the formation of BGs, whereas modulation of other Rab proteins involved in dynamic regulation of the endocytic-recycling pathway had no effect. Impairment of Rab11A function led to a missorting of Langerin to lysosomal compartments, but inhibition of Langerin degradation by chloroquine did not restore the formation of BGs. Loss of RCP, but not of Rip11, also had a modest, but reproducible effect on Langerin stability and BG biogenesis, pointing to a role for Rab11A-RCP complexes in these events. Our results show that Rab11A and Langerin are required for BG biogenesis, and they illustrate the role played by a Rab GTPase in the formation of a specialized subcompartment within the endocytic-recycling system.

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Section: Discussionmentioning

confidence: 96%

Rab11A Controls the Biogenesis of Birbeck Granules by Regulating Langerin Recycling and Stability

Uzan-Gafsou

Bausinger²,

Proamer³

et al. 2007

MBoC

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“…Through its effect on coat formation, BFA has also been shown to induce fusion and redistribution of the membranes of the early endocytic pathway and the trans-Golgi network (TGN), resulting in a continuous tubular network (Lippincott-Schwartz et al, 1991;Wood et al, 1991). Thus, we next examined the effect of BFA on the relationship between BGs and the endosomal system.…”

Section: Brefeldin a Induces Fusion Of Birbeck Granules With Other Comentioning

confidence: 99%

“…This requires their interaction with Arf exchange factors that catalyze the exchange of GDP for GTP, a process that can be inhibited by BFA (Donaldson et al, 1992a,b). The resultant inhibition of coat formation interrupts the membrane traffic regulatory functions they normally carry out (Lippincott-Schwartz et al, 1991;Klausner et al, 1992). In view of the known inhibitory effect of BFA on coat formation and the predominance of coated structures in the pericentriolar area, we reexamined the influence of BFA on Langerin recycling.…”

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confidence: 99%

Birbeck Granules Are Subdomains of Endosomal Recycling Compartment in Human Epidermal Langerhans Cells, Which Form Where Langerin Accumulates

Dermott

Ziylan

Spehner

et al. 2002

MBoC

169

155

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Birbeck granules are unusual rod-shaped structures specific to epidermal Langerhans cells, whose origin and function remain undetermined. We investigated the intracellular location and fate of Langerin, a protein implicated in Birbeck granule biogenesis, in human epidermal Langerhans cells. In the steady state, Langerin is predominantly found in the endosomal recycling compartment and in Birbeck granules. Langerin internalizes by classical receptor-mediated endocytosis and the first Birbeck granules accessible to endocytosed Langerin are those connected to recycling endosomes in the pericentriolar area, where Langerin accumulates. Drug-induced inhibition of endocytosis results in the appearance of abundant open-ended Birbeck granule-like structures appended to the plasma membrane, whereas inhibition of recycling induces Birbeck granules to merge with a tubular endosomal network. In mature Langerhans cells, Langerin traffic is abolished and the loss of internal Langerin is associated with a concomitant depletion of Birbeck granules. Our results demonstrate an exchange of Langerin between early endosomal compartments and the plasma membrane, with dynamic retention in the endosomal recycling compartment. They show that Birbeck granules are not endocytotic structures, rather they are subdomains of the endosomal recycling compartment that form where Langerin accumulates. Finally, our results implicate ADP-ribosylation factor proteins in Langerin trafficking and the exchange between Birbeck granules and other endosomal membranes. INTRODUCTIONLangerhans cells (LCs), the representatives of the dendritic cell lineage in the epidermis and mucosal tissues, capture antigen in the skin before migrating to the T-cell-dependent areas of draining lymph nodes. During this migration, they undergo a maturation process that allows them to present antigens to naive T cells (Kripke et al., 1990;Moll et al., 1993). Notably, Langerhans cells are the only epidermal cells to constitutively express major histocompatibility complex class II molecules (Klareskog et al., 1977;Rowden et al., 1977), CD1a molecules (Fithian et al., 1981), and Langerin (Valladeau et al., 2000) at their cell surface. In addition, Langerhans cells differ ultrastructurally from other dendritic cells through the presence of Birbeck granules (BGs), distinctive rod-shaped structures of variable length with a central, periodically striated lamella (Birbeck et al., 1961).Despite the use of "dynamic" electron microscope studies (reviewed in Schuler et al., 1991), Birbeck granules remain enigmatic. Specifically, conflicting theories exist regarding Article published online ahead of print. Mol. Biol. Cell 10.1091/ mbc.01-06-0300. Article and publication date are at www.molbiolcell.org/cgi/doi/10.1091/mbc.01-06-0300.† These authors contributed equally to this work and are listed in alphabetical order. # Corresponding author. E-mail address: daniel.hanau@efs-alsace.fr. Abbreviations used: Au, gold-labeled; BG, Birbeck granule; ERC, endosomal recycling compartment; Fi, freshl...

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“…In contrast, brefeldin A (BFA), which blocks the translocation of ARF-1 on membranes (Klausner et al, 1992) and the subsequent binding of AP-1 (Robinson and Kreis, 1992;Wong and Brodsky, 1992) and GGAs (Boman et al, 2000;Dell'Angelica et al, 2000;Hirst et al, 2000), results in the formation of a tubular network containing both TGN and endosomal markers (Lippincott-Schwartz et al, 1991). We then incubated the GFP-CI-MPR-expressing HeLa cells with BFA.…”

Section: Pi-3 Kinases Regulates Tgn-derived Tubule Formationmentioning

confidence: 99%

Visualization of TGN to Endosome Trafficking through Fluorescently Labeled MPR and AP-1 in Living Cells

Waguri

Dewitte

Borgne

et al. 2003

MBoC

182

169

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We have stably expressed in HeLa cells a chimeric protein made of the green fluorescent protein (GFP) fused to the transmembrane and cytoplasmic domains of the mannose 6-phosphate/insulin like growth factor II receptor in order to study its dynamics in living cells. At steady state, the bulk of this chimeric protein (GFP-CI-MPR) localizes to the trans-Golgi network (TGN), but significant amounts are also detected in peripheral, tubulo-vesicular structures and early endosomes as well as at the plasma membrane. Time-lapse videomicroscopy shows that the GFP-CI-MPR is ubiquitously detected in tubular elements that detach from the TGN and move toward the cell periphery, sometimes breaking into smaller tubular fragments. The formation of the TGN-derived tubules is temperature dependent, requires the presence of intact microtubule and actin networks, and is regulated by the ARF-1 GTPase. The TGN-derived tubules fuse with peripheral, tubulo-vesicular structures also containing the GFP-CI-MPR. These structures are highly dynamic, fusing with each other as well as with early endosomes. Time-lapse videomicroscopy performed on HeLa cells coexpressing the CFP-CI-MPR and the AP-1 complex whose ␥-subunit was fused to YFP shows that AP-1 is present not only on the TGN and peripheral CFP-CI-MPR containing structures but also on TGN-derived tubules containing the CFP-CI-MPR. The data support the notion that tubular elements can mediate MPR transport from the TGN to a peripheral, tubulo-vesicular network dynamically connected with the endocytic pathway and that the AP-1 coat may facilitate MPR sorting in the TGN and endosomes. INTRODUCTIONThe mannose 6-phosphate receptors (MPRs) are essential components for lysosome biogenesis and cellular homeostasis (Kornfeld, 1992;Ludwig et al., 1995). The primary function of the cation-independent and the cation-dependent mannose 6-phosphate receptors (CI-MPR and CD-MPR) is to sort newly synthesized lysosomal enzymes from the secretory pathway for subsequent transport to endosomal/lysosomal compartments. To carry out their function, the MPRs must bind the common mannose 6-phosphate recognition marker on soluble lysosomal enzymes in the trans-Golgi network (TGN), the last sorting station of the secretory pathway, and be packaged into TGN-derived transport intermediates. After budding, these transport intermediates fuse with endosomes where the MPRs unload their bound ligands. Although the lysosomal enzymes are transported to lysosomes, the MPRs are retrieved to the TGN or occasionally to the plasma membrane. Although the precise pathways followed by the MPRs at the exit of the TGN remain to be better defined, it has become clear during the past years that the sorting of MPRs from the compartments they visit, i.e., TGN, endosomes and plasma membrane, is directed by Article published online ahead of print. Mol. Biol. Cell 10.1091/ mbc.E02-06 -0338. Article and publication date are at www. molbiolcell.org/cgi/doi/10.1091/mbc.E02-06 -0338.□ V Online version of this article contains video material. ...

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Brefeldin A's effects on endosomes, lysosomes, and the TGN suggest a general mechanism for regulating organelle structure and membrane traffic

Cited by 799 publications

References 44 publications

Rab11A Controls the Biogenesis of Birbeck Granules by Regulating Langerin Recycling and Stability

Rab11A Controls the Biogenesis of Birbeck Granules by Regulating Langerin Recycling and Stability

Birbeck Granules Are Subdomains of Endosomal Recycling Compartment in Human Epidermal Langerhans Cells, Which Form Where Langerin Accumulates

Visualization of TGN to Endosome Trafficking through Fluorescently Labeled MPR and AP-1 in Living Cells

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