The trans‐SNARE complex VAMP4 /Stx6/Stx7/Vti1b is a key regulator of Golgi to late endosome MT1‐MMP transport in macrophages

Traffic ◽  
2021 ◽  
Author(s):  
Zoe Elizabeth West ◽  
Savannah Margaret Aitcheson ◽  
Annalese Barbara Trudy Semmler ◽  
Rachael Zoe Murray
Keyword(s):  
Late Endosome ◽  
Snare Complex

scholarly journals Syntaxin-17 delivers PINK1/parkin-dependent mitochondrial vesicles to the endolysosomal system

2016 ◽  
Vol 214 (3) ◽  
pp. 275-291 ◽  
Author(s):  
Gian-Luca McLelland ◽  
Sydney A. Lee ◽  
Heidi M. McBride ◽  
Edward A. Fon
Keyword(s):  
Common Ancestor ◽  
Vesicle Transport ◽  
Late Endosome ◽  
Snare Complex ◽  
Endomembrane System ◽  
Last Eukaryotic Common Ancestor ◽  
Transport Pathway ◽  
Attachment Protein ◽  
Mitochondrial Content ◽  
Protein Receptor

Mitochondria are considered autonomous organelles, physically separated from endocytic and biosynthetic pathways. However, recent work uncovered a PINK1/parkin-dependent vesicle transport pathway wherein oxidized or damaged mitochondrial content are selectively delivered to the late endosome/lysosome for degradation, providing evidence that mitochondria are indeed integrated within the endomembrane system. Given that mitochondria have not been shown to use canonical soluble NSF attachment protein receptor (SNARE) machinery for fusion, the mechanism by which mitochondrial-derived vesicles (MDVs) are targeted to the endosomal compartment has remained unclear. In this study, we identify syntaxin-17 as a core mitochondrial SNARE required for the delivery of stress-induced PINK1/parkin-dependent MDVs to the late endosome/lysosome. Syntaxin-17 remains associated with mature MDVs and forms a ternary SNARE complex with SNAP29 and VAMP7 to mediate MDV–endolysosome fusion in a manner dependent on the homotypic fusion and vacuole protein sorting (HOPS) tethering complex. Syntaxin-17 can be traced to the last eukaryotic common ancestor, hinting that the removal of damaged mitochondrial content may represent one of the earliest vesicle transport routes in the cell.

scholarly journals Syntaxin 7 Is Localized to Late Endosome Compartments, Associates with Vamp 8, and Is Required for Late Endosome–Lysosome Fusion

2000 ◽  
Vol 11 (9) ◽  
pp. 3137-3153 ◽  
Author(s):  
Barbara M. Mullock ◽  
Chez W. Smith ◽  
Gudrun Ihrke ◽  
Nicholas A. Bright ◽  
Margaret Lindsay ◽  
...  
Keyword(s):  
Late Endosome ◽  
Endocytic Pathway ◽  
Snare Complex ◽  
Rab Gtpase ◽  
Animal Cells ◽  
Protein Traffic ◽  
Late Endosomes ◽  
Molecular Machinery ◽  
Golgi Network

Protein traffic from the cell surface or thetrans-Golgi network reaches the lysosome via a series of endosomal compartments. One of the last steps in the endocytic pathway is the fusion of late endosomes with lysosomes. This process has been reconstituted in vitro and has been shown to require NSF, α and γ SNAP, and a Rab GTPase based on inhibition by Rab GDI. InSaccharomyces cerevisiae, fusion events to the lysosome-like vacuole are mediated by the syntaxin protein Vam3p, which is localized to the vacuolar membrane. In an effort to identify the molecular machinery that controls fusion events to the lysosome, we searched for mammalian homologues of Vam3p. One such candidate is syntaxin 7. Here we show that syntaxin 7 is concentrated in late endosomes and lysosomes. Coimmunoprecipitation experiments show that syntaxin 7 is associated with the endosomal v-SNARE Vamp 8, which partially colocalizes with syntaxin 7. Importantly, we show that syntaxin 7 is specifically required for the fusion of late endosomes with lysosomes in vitro, resulting in a hybrid organelle. Together, these data identify a SNARE complex that functions in the late endocytic system of animal cells.

scholarly journals Btn2, a Hook1 Ortholog and Potential Batten Disease-Related Protein, Mediates Late Endosome-Golgi Protein SortinginYeast

2007 ◽  
Vol 27 (2) ◽  
pp. 605-621 ◽  
Author(s):  
Rachel Kama ◽  
Micah Robinson ◽  
Jeffrey E. Gerst
Keyword(s):  
Golgi Apparatus ◽  
Protein Trafficking ◽  
Fluorescent Protein ◽  
Batten Disease ◽  
Specific Protein ◽  
Late Endosome ◽  
Snare Complex ◽  
Golgi Protein ◽  
Green Fluorescent

ABSTRACT BTN2 gene expression in the yeast Saccharomyces cerevisiae is up-regulated in response to the deletion of BTN1, which encodes the ortholog of a human Batten disease protein. We isolated Btn2 as a Snc1 v-SNARE binding protein using the two-hybrid assay and examined its role in intracellular protein trafficking. We show that Btn2 is an ortholog of theDrosophila and mammalian Hook1 proteins that interact with SNAREs, cargo proteins, and coat components involved in endosome-Golgi protein sorting. By immunoprecipitation, it was found that Btn2 bound the yeast endocytic SNARE complex (e.g., Snc1 and Snc2 [Snc1/2], Tlg1, Tlg2, and Vti1), the Snx4 sorting nexin, and retromer (e.g., Vps26 and Vps35). In in vitro binding assays, recombinant His6-tagged Btn2 bound glutathione S-transferase (GST)-Snc1 and GST-Vps26. Btn2-green fluorescent protein and Btn2-red fluorescent protein colocalize with Tlg2, Snx4, and Vps27 to a compartment adjacent to the vacuole that corresponds to a late endosome. The deletion of BTN2 blocks Yif1 retrieval back to the Golgi apparatus, while the localization of Ste2, Fur4, Snc1, Vps10, carboxypeptidases Y (CPY) and S (CPS), Sed5, and Sec7 is unaltered in btn2Δ cells. Yif1 delivery to the vacuole was observed in other late endosome-Golgi trafficking mutants, including ypt6Δ, snx4Δ, and vps26Δ cells. Thus, Btn2 facilitates specific protein retrieval from a late endosome to the Golgi apparatus, a process which may be adversely affected in patients with Batten disease.

The delivery of endocytosed cargo to lysosomes

2009 ◽  
Vol 37 (5) ◽  
pp. 1019-1021 ◽  
Author(s):  
J. Paul Luzio ◽  
Michael D.J. Parkinson ◽  
Sally R. Gray ◽  
Nicholas A. Bright
Keyword(s):  
Plasma Membrane ◽  
Mammalian Cells ◽  
Late Endosome ◽  
Snare Complex ◽  
Coated Pits ◽  
Free System ◽  
Endosomal Sorting ◽  
Protein Receptor ◽  
Late Endosomes ◽  
Early Endosomes

In mammalian cells, endocytosed cargo that is internalized through clathrin-coated pits/vesicles passes through early endosomes and then to late endosomes, before delivery to lysosomes for degradation by proteases. Late endosomes are MVBs (multivesicular bodies) with ubiquitinated membrane proteins destined for lysosomal degradation being sorted into their luminal vesicles by the ESCRT (endosomal sorting complex required for transport) machinery. Cargo is delivered from late endosomes to lysosomes by kissing and direct fusion. These processes have been studied in live cell experiments and a cell-free system. Late endosome–lysosome fusion is preceded by tethering that probably requires mammalian orthologues of the yeast HOPS (homotypic fusion and vacuole protein sorting) complex. Heterotypic late endosome–lysosome membrane fusion is mediated by a trans-SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex comprising Syntaxin7, Vti1b, Syntaxin8 and VAMP7 (vesicle-associated membrane protein 7). This differs from the trans-SNARE complex required for homotypic late endosome fusion in which VAMP8 replaces VAMP7. VAMP7 is also required for lysosome fusion with the plasma membrane and its retrieval from the plasma membrane to lysosomes is mediated by its folded N-terminal longin domain. Co-ordinated interaction of the ESCRT, HOPS and SNARE complexes is required for cargo delivery to lysosomes.

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