Of the vacuolar protein sorting (VPS) mutants, 15
fall into the class E group. The class E mutants accumulate vacuolar,
endocytic and late Golgi markers in an aberrant endosomal structure,
the class E compartment. Several of the class E gene products have
been shown to form a large endosome-associated complex that is
required for normal endosome function. The assembly of this complex
appears to be regulated by a 350 kDa soluble complex that contains the
class E proteins Vps23p and Vps28p, referred to as the regulator of
the endosomal maturation complex (EMC-R). Vps23 is a homolog of the
mammalian tumor susceptibility gene 101 (TSG101) which has recently
been shown to be involved in the formation of late endosome
multi-vesicular bodies (MVBs), a step required for the down-regulation
of signaling cell-surface receptors. The homology of Vps23p and TSG101
is conserved throughout several interesting motifs, including an
ubiquitin-conjugating enzyme-like domain. Biochemical purification of
the EMC-R indicated the presence a novel 25 kDa subunit. The identity
of this 25kDa band was revealed by MALDI mass spectroscopy to be the
product of SRN2. Deletion of SRN2 disrupts the EMC-R and
therefore gives rise to cells that display a class E compartment and
missort numerous cargoes destined for the vacuole. Data indicate that
the EMC-R regulates the MVB pathway by driving vesicle invagination
and/or cargo selection.
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