Lysosome Associated Membrane Protein 1 (Lamp1) Traffics Directly from the TGN to Early Endosomes

Cook, Neil R.; Row, Paula E.; Davidson, Howard W.

doi:10.1111/j.1600-0854.2004.00212.x

Cited by 85 publications

(71 citation statements)

References 60 publications

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“…Our data also show that the LAMP carrier pathway is not the only TGN exit for LAMPs. In addition to LAMP carriers, we found TGN-bound LAMP in clathrincoated membranes 13,14 , which is in agreement with previous EM studies and observations showing that LAMPs can traffic directly from the TGN to early endosomes 53 . However, in contrast to CI-MPR, LAMPs were not or only moderately concentrated in clathrin-coated TGN membranes.…”

Section: Nature Communications | Doisupporting

confidence: 81%

hVps41 and VAMP7 function in direct TGN to late endosome transport of lysosomal membrane proteins

et al. 2013

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Targeted delivery of lysosome-associated membrane proteins is important for lysosome stability and function. Here we identify a pathway for transport of lysosome-associated membrane proteins directly from the trans-Golgi network to late endosomes, which exists in parallel to mannose 6-phosphate receptor and clathrin-dependent transport of lysosomal enzymes to early endosomes. By immunoelectron microscopy we localized endogenous LAMP-1 and -2 as well as LAMP-1-mGFP to non-coated, biosynthetic carriers at the transGolgi network and near late endosomes. These LAMP carriers were negative for mannose 6-phosphate receptor, adaptor-protein complex-1, secretory albumin and endocytic markers, but contained the homotypic fusion and protein sorting complex component hVps41 and the soluble N-ethylmaleimide-sensitive factor attachment protein receptors protein VAMP7. Knockdown of hVps41 or VAMP7 resulted in the accumulation of lysosome-associated membrane protein carriers, whereas knockdown of hVps39 or hVps18 did not, indicating that the effect of hVps41 is independent of CORVET/HOPS. Mannose 6-phosphate receptor carriers remained unaffected upon hVps41 or VAMP7 knockdown, implicating that hVps41 and VAMP7 are specifically involved in the fusion of trans-Golgi network-derived lysosomeassociated membrane protein carriers with late endosomes.

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Section: Nature Communications | Doisupporting

confidence: 81%

hVps41 and VAMP7 function in direct TGN to late endosome transport of lysosomal membrane proteins

et al. 2013

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“…However, clavesin knockdown in hippocampal neurons did cause a significant enlargement of a LAMP1-positive compartment. LAMP1 traffics from the TGN to early endosomes before progression into late endosomes/lysosomes (40). Given the lack of influence of clavesin knockdown on TGN to endosome trafficking, these data suggest that clavesins function in a pathway between early endosomes and mature lysosomes.…”

Section: Discussionmentioning

confidence: 91%

“…Thus, alterations in the localization of the mannose 6-phosphate receptor are indicative of disruptions in the TGN/endosomal trafficking cycle. In contrast, LAMP1 is a resident late endosome/lysosomal protein that is delivered in a clathrin-independent manner from the TGN to early endosomes, which then transition into late endosomes/lysosomes (40,41). Cultured hippocampal neurons were transduced with a control virus encoding a nontargeting sequence or with viruses encoding two sequences specific for clavesin 1 and two sequences specific for clavesin 2.…”

Section: Resultsmentioning

confidence: 99%

The Clavesin Family, Neuron-specific Lipid- and Clathrin-binding Sec14 Proteins Regulating Lysosomal Morphology

Katoh

Ritter

Gaffry

et al. 2009

Journal of Biological Chemistry

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Clathrin-coated vesicles (CCVs) originating from the transGolgi network (TGN) provide a major transport pathway from the secretory system to endosomes/lysosomes. Herein we describe paralogous Sec14 domain-bearing proteins, clavesin 1/CRALBPL and clavesin 2, identified through a proteomic analysis of CCVs. Clavesins are enriched on CCVs and form a complex with clathrin heavy chain (CHC) and adaptor protein-1, major coat components of TGN-derived CCVs. The proteins co-localize with markers of endosomes and the TGN as well as with CHC and adaptor protein-1. A membrane mimic assay using the Sec14 domain of clavesin 1 reveals phosphatidylinositol 3,5-bisphosphate as a specific lipid partner. Phosphatidylinositol 3,5-bisphosphate is localized to late endosomes/lysosomes, and interestingly, isoform-specific knockdown of clavesins in neurons using lentiviral delivery of interfering RNA leads to enlargement of a lysosome-associated membrane protein 1-positive membrane compartment with no obvious influence on the CCV machinery at the TGN. Since clavesins are expressed exclusively in neurons, this new protein family appears to provide a unique neuron-specific regulation of late endosome/lysosome morphology.

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“…Taken together, these data suggest that urease-derived ammonia may enhance fusion of nascent Hp phagosomes with EEA1-positive endosomes, and phagosome accumulation of EEA1 may, in turn, facilitate the phagosome clustering and fusion required for megasome formation. In addition to its role as a regulator of endosome size, EEA1 is also required for delivery of newly synthesized lysosomal membrane glycoproteins to early endosomes from the trans-Golgi network [61,62]. Thus, retention of EEA1 on wild-type Hp phagosomes may allow these compartments to acquire small amounts of lamp-1 directly from the biosynthetic pathway in peritoneal macrophages without concomitant phagosome acidification or acquisition of other late endosome/lysosome markers.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, retention of EEA1 on wild-type Hp phagosomes may allow these compartments to acquire small amounts of lamp-1 directly from the biosynthetic pathway in peritoneal macrophages without concomitant phagosome acidification or acquisition of other late endosome/lysosome markers. Conversely, J774 and RAW264.7 cells may resemble HeLa cells, wherein newly synthesized lamp-1 is targeted directly to late endosomes [61]. Regardless of the mechanism, the absence of lamp-1 on Hp megasomes in macrophage cell lines facilitated analysis of the mutant phenotype.…”

Section: Discussionmentioning

confidence: 99%

Role of urease in megasome formation and Helicobacter pylori survival in macrophages

Schwartz

Allen

2006

Journal of Leukocyte Biology

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Previous studies have demonstrated that Helicobacter pylori (Hp) delays its entry into macrophages and persists inside megasomes, which are poorly acidified and accumulate early endosome autoantigen 1. Herein, we explored the role of Hp urease in bacterial survival in murine peritoneal macrophages and J774 cells. Plasmid-free mutagenesis was used to replace ureA and ureB with cat in Hp Strains 11637 and 11916. ureAB null Hp lacked detectable urease activity and did not express UreA or UreB as judged by immunoblotting. Deletion of ureAB had no effect on Hp binding to macrophages or the rate or extent of phagocytosis. However, intracellular survival of mutant organisms was impaired significantly. Immunofluorescence microscopy demonstrated that (in contrast to parental organisms) mutant Hp resided in single phagosomes, which were acidic and accumulated the lysosome marker lysosome-associated membrane protein-1 but not early endosome autoantigen 1. A similar phenotype was observed for spontaneous urease mutants derived from Hp Strain 60190. Treatment of macrophages with bafilomycin A1, NH 4 Cl, or chloroquine prevented acidification of phagosomes containing mutant Hp. However, only ammonium chloride enhanced bacterial viability significantly. Rescue of ureAB null organisms was also achieved by surface adsorption of active urease. Altogether, our data indicate a role for urease and urease-derived ammonia in megasome formation and Hp survival.

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Lysosome Associated Membrane Protein 1 (Lamp1) Traffics Directly from the TGN to Early Endosomes

Cited by 85 publications

References 60 publications

hVps41 and VAMP7 function in direct TGN to late endosome transport of lysosomal membrane proteins

hVps41 and VAMP7 function in direct TGN to late endosome transport of lysosomal membrane proteins

The Clavesin Family, Neuron-specific Lipid- and Clathrin-binding Sec14 Proteins Regulating Lysosomal Morphology

Role of urease in megasome formation and Helicobacter pylori survival in macrophages

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