Longins and their longin domains: regulated SNAREs and multifunctional SNARE regulators

Rossi, Valeria; Banfield, David K; Vacca, Marcella; Dietrich, Lars E. P.; Ungermann, Christian; D’Esposito, Maurizio; Galli, Thierry; Filippini, F.

doi:10.1016/j.tibs.2004.10.002

Cited by 148 publications

(170 citation statements)

References 81 publications

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“…Because residues 134-166 of SPE-39 are predicted to constitute an ␣-helix that can potentially form coiled-coil bundles with other ␣-helices (Lupas et al, 1991), a GST-VAMP7 fusion protein was included as a control to further demonstrate the specificity of this assay. The GST-VAMP7 fusion protein contains the first 190 residues of mouse VAMP7, which include two coiled-coil regions: the regulatory longin domain and the core SNARE motif (reviewed by Rossi et al, 2004). No interactions of GST-VAMP7 with either MBP-CeVPS33A or MBP-CeVPS33B (Figure 2, B and C, lane 3) were detected, suggesting that the observed interaction between SPE-39 and the VPS33 homologues was specific and did not result from nonspecific coiled-coil pairing.…”

Section: Spe-39 Binds C Elegans Vps33a and Vps33b In Vitromentioning

confidence: 99%

SPE-39 Family Proteins Interact with the HOPS Complex and Function in Lysosomal Delivery

Zhu

Salazar²,

Zlatic³

et al. 2009

MBoC

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Yeast and animal homotypic fusion and vacuole protein sorting (HOPS) complexes contain conserved subunits, but HOPS-mediated traffic in animals might require additional proteins. Here, we demonstrate that SPE-39 homologues, which are found only in animals, are present in RAB5-, RAB7-, and RAB11-positive endosomes where they play a conserved role in lysosomal delivery and probably function via their interaction with the core HOPS complex. Although Caenorhabditis elegans spe-39 mutants were initially identified as having abnormal vesicular biogenesis during spermatogenesis, we show that these mutants also have disrupted processing of endocytosed proteins in oocytes and coelomocytes. C. elegans SPE-39 interacts in vitro with both VPS33A and VPS33B, whereas RNA interference of VPS33B causes spe-39-like spermatogenesis defects. The human SPE-39 orthologue C14orf133 also interacts with VPS33 homologues and both coimmunoprecipitates and cosediments with other HOPS subunits. SPE-39 knockdown in cultured human cells altered the morphology of syntaxin 7-, syntaxin 8-, and syntaxin 13-positive endosomes. These effects occurred concomitantly with delayed mannose 6-phosphate receptor-mediated cathepsin D delivery and degradation of internalized epidermal growth factor receptors. Our findings establish that SPE-39 proteins are a previously unrecognized regulator of lysosomal delivery and that C. elegans spermatogenesis is an experimental system useful for identifying conserved regulators of metazoan lysosomal biogenesis. INTRODUCTIONLysosome biogenesis is mediated by multiple vesicular budding and fusion events that deliver components between subcellular compartments (Luzio et al., 2003). In Saccharomyces cerevisiae, vesicular fusion at the vacuole (the yeast equivalent of lysosomes) requires the homotypic fusion and vacuole protein sorting (HOPS) complex, which regulates vesicle docking through its interaction with soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (SNAREs) and the Rab protein Ypt7p Sato et al., 2000;Wurmser et al., 2000). The yeast HOPS complex contains class C Vps proteins Vps11p, Vps16p, Vps18p, and Vps33p (Rieder and Emr, 1997) and class B Vps proteins Vps39p and Vps41p (Seals et al., 2000;Wurmser et al., 2000). In addition to vesicular fusion at the vacuole, the class C Vps proteins also function in Golgi-to-endosome transport and other steps in vacuolar delivery pathways (Srivastava et al., 2000;Peterson and Emr, 2001;Subramanian et al., 2004;Peplowska et al., 2007). Involvement of the class C Vps proteins at multiple stages has also been reported in mammalian cells (Kim et al., 2003;Richardson et al., 2004). Vesicular trafficking to the lysosome has been extensively described in yeast (Bowers and Stevens, 2005), but it is also known that this process is more complex in metazoans (Dell'Angelica, 2004). Yeast only has lysosomes of a single type, whereas animals have lysosomes and lysosome-related organelles that are functionally diverse. This diversity is evident when comparing th...

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Section: Spe-39 Binds C Elegans Vps33a and Vps33b In Vitromentioning

confidence: 99%

SPE-39 Family Proteins Interact with the HOPS Complex and Function in Lysosomal Delivery

Zhu

Salazar²,

Zlatic³

et al. 2009

MBoC

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“…178 Such a domain has been identified in several trafficking proteins, including the SNAREs Ykt6, Nyv1 and Sec22, the s-subunit of the AP-complexes, and several subunits of the TRAPP complex. 179,180 So far, one study has addressed the role of Mon1 and Ccz1 in the fusion reaction. Vacuole fusion is strongly affected if either protein is missing or if the proteins are inhibited by specific antibodies.…”

Section: The Vacuole Fusion Machinerymentioning

confidence: 99%

Yeast vacuole fusion: A model system for eukaryotic endomembrane dynamics

Ostrowicz¹,

Meiringer²,

Ungermann³

2008

Autophagy

101

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Vesicular transport in eukaryotic cells is concluded with the consumption of the vesicle at the target membrane. This fusion process relies on Rabs, tethers and SNAREs. Powerful in vitro fusion systems using isolated organelles were crucial to obtain insights into the underlying mechanism of membrane fusionfrom the initiation of fusion to lipid bilayer mixing. Among these systems, yeast vacuoles turned out to be particularly useful as they can be manipulated biochemically and genetically. Studies relying on this organelle have revealed insights into the connection of vacuole fusion to endomembrane biogenesis. A number of fusion factors were identified and characterized over the last several years, and placed into the fusion cascade. Within this review, we will present and discuss the current state of our knowledge on vacuole fusion.

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“…The longin fold consists of five central ␤-sheets sandwiched by two ␣-helices on one face and one ␣-helix on the opposite face (Gonzalez et al, 2001;Tochio et al, 2001). Three longin proteins have been characterized in detail: Sec22 is required for trafficking between the ER and the Golgi, and for transport within the Golgi; Ykt6 is required along the Golgi, in endosomes and in the vacuole/lysosome system; and Ti-VAMP is required in neuronal cells (Rossi et al, 2004). The distribution of Sec22 and Ykt6 across the endomembrane system in yeast suggests that longins have a general role along the secretory pathway and in fusion reactions.…”

Section: Structure Of Snaresmentioning

confidence: 99%