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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Purpose. To determine if left ventricular or inferior vena cava (IVC) measurements are easier to obtain on point-of-care ultrasound by anesthesiologists in preoperative patients, and to assess the relationship between preoperative cardiac dimensions and hypotension with the induction of general anesthesia. Methods. This prospective observational study was conducted at a large academic medical center. Sixty-three patients undergoing noncardiac surgeries under general anesthesia were enrolled. Ultrasound examinations were performed by anesthesiologists in the preoperative area. To ensure that hypotension represented both a relative and absolute decrease in blood pressure, both a mean arterial pressure (MAP) < 65 mmHg and a MAP decrease of >30% from preoperative value defined this outcome. Results. Left ventricular measurements were more likely to be acquired than IVC measurements (97% vs. 79%). Subjects without adequate images to assess IVC collapsibility tended to have a higher body mass index (33.6 ± 5.5 vs. 28.5 ± 4.5, p = 0.001 ). While high left ventricular end-diastolic diameter values were associated with a decreased odds of MAP < 65 mmHg (OR: 0.24, 95% CI: 0.07–0.83, p = 0.023 ) or a MAP decrease of >30% from baseline alone (OR: 0.25, 95% CI: 0.07–0.83, p = 0.023 ), the primary endpoint of both relative and absolute hypotension was not associated with preoperative left ventricular dimensions. Conclusions. Preoperative cardiac ultrasound may be a more reliable way for anesthesiologists to assess patients’ volume status compared to ultrasound of the IVC, particularly for patients with a higher body mass index.

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