AspergillusRabB^Rab5Integrates Acquisition of Degradative Identity with the Long Distance Movement of Early Endosomes

Abstract

Of the two Aspergillus early endosomal Rab5 paralogues, RabB recruits, in its GTP conformation, Vps19, Vps45, and Vps34, and the CORVET complex and couples acquisition of PI(3)P degradative identity with the long-distance movement of early endosomes. RabA also recruits CORVET, albeit less efficiently. The simultaneous loss of RabA and RabB is lethal.

CORVET and HOPS tethering complexes–coordinators of endosome and lysosome fusion

“…It later turned out that the four proteins function together along the endocytic pathway also in metazoan cells (Peterson and Emr, 2001;Richardson et al, 2004;Sriram et al, 2003;Rieder and Emr, 1997;Srivastava et al, 2000), although they are part of two complexes in yeast -CORVET (Peplowska et al, 2007) and HOPS Wurmser et al, 2000) ( Fig. 2A) which was nicely confirmed in the fungus Aspergillus nidulans (Abenza et al, 2010;Abenza et al, 2012). In agreement with a shared function of the four class C proteins, deletion of the remaining two subunits of either complex is less dramatic (Horazdovsky et al, 1996;Markgraf et al, 2009;Nakamura et al, 1997;Raymond et al, 1992;Raymond et al, 1990;Wada et al, 1992), suggesting that there is some functional redundancy of HOPS and CORVET within the endocytic pathway.…”

“…In agreement with a shared function of the four class C proteins, deletion of the remaining two subunits of either complex is less dramatic (Horazdovsky et al, 1996;Markgraf et al, 2009;Nakamura et al, 1997;Raymond et al, 1992;Raymond et al, 1990;Wada et al, 1992), suggesting that there is some functional redundancy of HOPS and CORVET within the endocytic pathway. In addition to the four shared class C proteins, CORVET contains two Rab5-binding subunits, Vps3 and Vps8, whereas HOPS has instead the Rab7-binding subunits Vps39 and Vps41 (also known as Vam6 and Vam2) (Abenza et al, 2010;Abenza et al, 2012;Markgraf et al, 2009;Peplowska et al, 2007;Price et al, 2000;Seals et al, 2000;Wurmser et al, 2000). The similarity between HOPS and CORVET suggests that intermediate complexes also exist, and indeed a complex of low abundance can be isolated that consists of the class C subunits, plus HOPS Vps41 and CORVET Vps3 Peplowska et al, 2007) (Fig.…”

“…The identification of the yeast CORVET complex as a heterohexamer could then explain both the severe phenotype of the class C mutants and their link to Vps8 and Vps3 (Peplowska et al, 2007). CORVET is an effector of Rab5 both in yeast and Aspergillus (Peplowska et al, 2007;Abenza et al, 2010;Balderhaar et al, 2013). Both Vps8 and Vps3 bind to the yeast Rab5-like Vps21 protein (Horazdovsky et al, 1996;Markgraf et al, 2009;Pawelec et al, 2010;Plemel et al, 2011), and their deletion results in a large vacuole in yeast (Banta et al, 1988;Raymond et al, 1992).…”

“…In addition, and probably later on, Rab7 also promotes fusion with the lysosome, although the exact order has not been clarified (Balderhaar et al, 2010;Huotari and Helenius, 2011;Liu et al, 2012). Intriguingly, Rab5 and Rab7 bind to two hexameric tethering complexes, the endosomal CORVET ('class C core vacuole/endosome tethering') and the late endosomal/lysosomal HOPS ('homotypic fusion and protein sorting') complex (Abenza et al, 2010;Abenza et al, 2012;Bröcker et al, 2012;Ostrowicz et al, 2010;Peplowska et al, 2007;Seals et al, 2000;Wurmser et al, 2000) ( Fig. 1; Fig.…”

Failure of lysosome clustering and positioning in the juxtanuclear region in cells deficient in rapsyn

“…S2C). Previous studies have shown that Rab7 is involved in the fusion of lysosomes by binding to the homotypic fusion and protein sorting (HOPS) complex (Wurmser et al, 2000;Abenza et al, 2010Abenza et al, , 2012Ostrowicz et al, 2010;Balderhaar and Ungermann, 2013). Thus, it is possible that rapsyn also promotes the clustering of Rab7 either directly or indirectly through its association with the Rabring 7 effector as implied by its colocalization with Rab7.…”