Budding yeast Ist1 is involved in a late step in sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles []. This entry also includes Ist1 homologues from animals and plants. Human Ist1 functions in the ESCRT (endosomal sorting complexes required for transport) pathway and is required for efficient abscission during HeLa cell cytokinesis []. Human Ist1 binds the transport (MIT) domain of VPS4, LIP5, and Spartin via its C-terminal MIT-interacting motif (MIM) [].
The endosomal sorting complex required for transport (ESCRT) machinery functions in several important eukaryotic cellular processes such as MVB (multivesicular body) formation. The AAA-ATPase Vps4 catalyzes disassembly of the ESCRT-III complex and may regulate membrane deformation and vesicle scission as well. Ist1 acts as a negative regulator of the MVB pathway by binding to the N-terminal MIT (microtubule interacting and transport) domain of Vps4 through its C-terminal region, with its 15 amino acids bearing strong homology to a conserved sequence motif called MIM1 (MIT interacting motif 1 []). This MIT domain is found in various proteins and enzymes including ubiquitin hydrolases proteases, ATPases (Spastin and VPS4 proteins) and ATPase activators (Vta1p/LIP5) [].
