Re-routing of the invariant chain to the direct sorting pathway by introduction of an AP3-binding motif from LIMP II

Gupta, Shailly N.; Kloster, Martine Müller; Rodionov, Dmitriy; Bakke, Oddmund

doi:10.1016/j.ejcb.2006.02.001

Cited by 19 publications

(17 citation statements)

References 67 publications

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“…10B). AP-3 has been thought to be involved in the transport in the latter part of the endocytic pathway ) but also at the TGN (Gupta et al, 2006). We found no effect on the half-life of Lamp1 (Fig.…”

Section: Depletion Of Rab7b Increases Ap-3 Levels Without Affecting Icontrasting

confidence: 38%

Rab7b controls trafficking from endosomes to the TGN

Progida

Cogli

Piro

et al. 2010

Journal of Cell Science

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108

113

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Rab7b is a recently identified member of the Rab GTPase protein family and has high similarity to Rab7. It has been reported that Rab7b is lysosome associated, that it is involved in monocytic differentiation and that it promotes lysosomal degradation of TLR4 and TLR9. Here we investigated further the localization and function of this GTPase. We found that wild-type Rab7b is lysosome associated whereas an activated, GTP-bound form of Rab7b localizes to the Golgi apparatus. In contrast to Rab7, Rab7b is not involved in EGF and EGFR degradation. Depletion of Rab7b or expression of Rab7b T22N, a Rab7b dominant-negative mutant, impairs cathepsin-D maturation and causes increased secretion of hexosaminidase. Moreover, expression of Rab7b T22N or depletion of Rab7b alters TGN46 distribution, cation-independent mannose-6-phosphate receptor (CI-MPR) trafficking, and causes an increase in the levels of the late endosomal markers CI-MPR and cathepsin D. Vesicular stomatitis virus G protein (VSV-G) trafficking, by contrast, is normal in Rab7b-depleted or Rab7b-T22N-expressing cells. In addition, depletion of Rab7b prevents cholera toxin B-subunit from reaching the Golgi. Altogether, these data indicate that Rab7b is required for normal lysosome function, and, in particular, that it is an essential factor for retrograde transport from endosomes to the trans-Golgi network (TGN).

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Section: Depletion Of Rab7b Increases Ap-3 Levels Without Affecting Icontrasting

confidence: 38%

Rab7b controls trafficking from endosomes to the TGN

Progida

Cogli

Piro

et al. 2010

Journal of Cell Science

Self Cite

108

113

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“…To examine the role of dynamin and AP180 in pMHC-II internalization we expressed dominant-negative forms of HA-tagged dynamin or GFP-AP180 in HeLa-CIITA, human B cells, and KG-1 DCs. Each of these reagents has been shown to effectively block clathrin-mediated endocytosis and lead to an accumulation of cargo proteins at the cell surface (21,37,38). Similar to the depletion of clathrin or AP-2, introduction of either dominant-negative dynamin or AP180 into HeLa-CIITA cells dramatically enhanced expression of MHC-II-Ii at the cell surface (Fig.…”

Section: Pmhc-ii and Mhc-ii-ii Complexes Internalize Andmentioning

confidence: 84%

Major Histocompatibility Complex Class II-Peptide Complexes Internalize Using a Clathrin- and Dynamin-independent Endocytosis Pathway

Walseng

Bakke

Roche

2008

Journal of Biological Chemistry

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117

121

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Major histocompatibility complex (MHC) class II molecules (MHC-II) function by binding antigenic peptides and displaying these peptides on the surface of antigen presenting cells (APCs) for recognition by peptide-MHC-II (pMHC-II)-specific CD4 T cells. It is known that cell surface MHC-II can internalize, exchange antigenic peptides in endosomes, and rapidly recycle back to the plasma membrane; however, the molecular machinery and trafficking pathways utilized by internalizing/recycling MHC-II have not been identified. We now demonstrate that unlike newly synthesized invariant chain-associated MHC-II, mature cell surface pMHC-II complexes internalize following clathrin-, AP-2-, and dynamin-independent endocytosis pathways. Immunofluorescence microscopy of MHC-II expressing HeLa-CIITA cells, human B cells, and human DCs revealed that pMHC enters Arf6 ؉ Rab35 ؉ EHD1 ؉ tubular endosomes following endocytosis. These data contrast the internalization pathways followed by newly synthesized and peptide-loaded MHC-II molecules and demonstrates that cell surface pMHC-II internalize and rapidly recycle from early endocytic compartments in tubular endosomes.

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“…22,29 Studies of lysosome-associated membrane proteins (LAMPs) and lysosome integral membrane proteins (LIMPs) have highlighted AP3 as the prime candidate for association with lysosome-targeting motifs to mediate the transport of protein to the lysosomes. 32,46 Therefore, internalized c-Mpl is likely routed to the lysosomes via interactions between AP3 and Y 8 RRL, and this interaction may be responsible for the rapid degradation of c-Mpl after Tpo stimulation. Although recent colocalization studies suggested that c-Mpl is not present in lysosomes, 47 we have found that the Tpo-stimulated rapid degradation of the receptor can be significantly inhibited by NHCl 4 , strongly suggesting that there is in fact a role for lysosomal degradation in controlling c-Mpl expression.…”

Section: Discussionmentioning

confidence: 99%

YRRL motifs in the cytoplasmic domain of the thrombopoietin receptor regulate receptor internalization and degradation

Hitchcock

Chen

King

et al. 2008

Blood

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IntroductionThrombopoietin (Tpo) is critical for the maintenance of hematopoietic stem and progenitor cells and is also the primary regulator of megakaryocyte development. 1,2 The binding of Tpo to its receptor, c-Mpl, causes associated Janus kinase 2 (Jak2) activation, which in turn phosphorylates (activates) several downstream effectors including signal transducers and activators of transcription (STAT) 3 and 5, mitogen-activated protein kinase (MAPK), phosphotidylinositol-3-kinase (PI3-K), and protein kinase C (PKC). [3][4][5][6][7] Activation of these pathways promotes proliferation and survival in c-Mplexpressing cell lines and hematopoietic progenitor cells, in addition to megakaryocyte lineage differentiation and maturation. [8][9][10][11] It is critical that Tpo signal transduction is stringently controlled to prevent uncontrolled proliferation. Suppressors of cytokine signaling (SOCS) proteins, phosphatases, and negative regulators such FAK, Lnk, and Lyn have all been shown to down-modulate Tpo-induced signaling. [12][13][14][15] However, the most effective method of regulating Tpo signaling is by controlling expression of c-Mpl on the plasma membrane. Tpo-mediated c-Mpl endocytosis, recycling, and degradation are rapid mechanisms to control signaling longevity and represent a mechanism that regulates Tpo signaling without new protein expression.The principal mechanism of receptor-mediated endocytosis in eukaryotic cells is the clathrin-coated vesicle. 16 Soluble clathrin molecules self-assemble and are recruited to the plasma membrane, where they form lattice structures and interact with transmembrane receptors via adaptor proteins (APs), such as AP2, to form clathrin-coated pits. 17,18 These pits then further invaginate before finally budding from the membrane to form clathrin-coated vesicles. AP2 is a heterotetramer composed of ␣2, ␤2, 2, and 2 subunits. The ␣2 and ␤2 subunits localize AP2 to the membrane, recruit endocytic accessory proteins, and bind clathrin heavy chain. [19][20][21] Transmembrane proteins are associated with the AP2-clathrin complex via the 2 domain, which binds directly to cytoplasmic YXX⌽ (where X ϭ any amino acid and ⌽ ϭ bulky hydrophobic residue) and [DE]XXX-L[IL] motifs. 22,23 To ensure that AP2 specifically associates with membrane-bound proteins, phosphorylation of 156 Thr in the 2 subunit results in a conformational change in AP2, dramatically increasing the affinity of 2 for YXX⌽ motifs. 24,25 156 Thr is phosphorylated by adaptor-associated kinase 1 (AAK1), 26 the activity of which is maximized by its association with clathrin, 27,28 ensuring that AP2-cargo protein interactions are initiated only at the plasma membrane. In addition to being an endocytic signal, YXX⌽ motifs located between 6 to 9 amino acids from the transmembrane domain mediate targeting of cargo protein to the lysosome and lysosome-like organelles via interactions with AP3. [29][30][31][32] c Methods Chemicals and reagentsPharmacologic inhibitors JakI, LY294002, SU6656, and U0126 where all purchased f...

show abstract

Re-routing of the invariant chain to the direct sorting pathway by introduction of an AP3-binding motif from LIMP II

Cited by 19 publications

References 67 publications

Rab7b controls trafficking from endosomes to the TGN

Rab7b controls trafficking from endosomes to the TGN

Major Histocompatibility Complex Class II-Peptide Complexes Internalize Using a Clathrin- and Dynamin-independent Endocytosis Pathway

YRRL motifs in the cytoplasmic domain of the thrombopoietin receptor regulate receptor internalization and degradation

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