The CORVET Tethering Complex Interacts with the Yeast Rab5 Homolog Vps21 and Is Involved in Endo-Lysosomal Biogenesis

Abstract

The dynamic equilibrium between vesicle fission and fusion at Golgi, endosome, and vacuole/lysosome is critical for the maintenance of organelle identity. It depends, among others, on Rab GTPases and tethering factors, whose function and regulation are still unclear. We now show that transport among Golgi, endosome, and vacuole is controlled by two homologous tethering complexes, the previously identified HOPS complex at the vacuole and a novel endosomal tethering (CORVET) complex, which interacts with the Rab GTPase Vps21. Both complexes share the four class C Vps proteins: Vps11, Vps16, Vps18, and Vps33. The HOPS complex, in addition, contains Vps41/Vam2 and Vam6, whereas the CORVET complex has the Vps41 homolog Vps8 and the (h)Vam6 homolog Vps3. Strikingly, the CORVET and HOPS complexes can interconvert; we identify two additional intermediate complexes, both consisting of the class C core bound to Vam6-Vps8 or Vps3-Vps41. Our data suggest that modular assembled tethering complexes define organelle biogenesis in the endocytic pathway.

Counting molecules in single organelles with superresolution microscopy allows tracking of the endosome maturation trajectory

“…In mammalian cells, the key proteins in this process are EEA1 (homolog of yeast Fab1), which binds to PI3P (34,42) and is thought to recruit and to effect Rab5 (homolog of yeast Vps21) (10). Rab5 in turn tethers vesicles (16,37) and interacts with the fusion complex CORVET (43) and through EEA1 with SNARE (44). However, owing to the lack of a direct measurement, it is still debated whether PI3P is produced on incoming vesicles, fused vesicles, or endosomes.…”

Functional Separation of Endosomal Fusion Factors and the Class C Core Vacuole/Endosome Tethering (CORVET) Complex in Endosome Biogenesis

“…On the basis of its homology to HOPS, the CORVET complex has been postulated to act as a tethering complex as well (2,4,12,14). However, it has remained challenging to find solid evidence supporting such a function.…”

“…This tethering machinery interacts with the SNARE Pep12 and its Sec1/Munc18 protein Vps45 to fuse transport vesicles at the endosomes (9,11,13,24). Additional fusion events at the early and late endosome may require the CORVET complex (12,14) (Fig. 1A).…”

“…Within the secretory pathway, CATCHR (complexes associated with tethering containing helical rods) complexes like the exocyst at the plasma membrane and the COG (conserved oligomeric Golgi) complex at the Golgi have been identified, whereas the Vps class C complexes, namely the CORVET and the HOPS (homotypic fusion and vacuole protein sorting) complexes, are necessary within the endolysosomal system (5, 7, 16 -18). CORVET and HOPS are both heterohexamer complexes that share the Vps11, Vps16, Vps18, and Vps33 subunits (8,10,12). Because of their inclusion in two tethering complexes, their deletions result in a massive fragmentation of the vacuole, which has been termed class C phenotype (Fig.…”

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

“…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).…”