Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking

Corrigendum: RILP interacts with HOPS complex via VPS41 subunit to regulate endocytic trafficking

The HOPS complex serves as a tethering complex with GEF activity for Ypt7p in yeast to regulate late endosomal membrane maturation. While the role of HOPS complex is well established in yeast cells, its functional and mechanistic aspects in mammalian cells are less well defined. In this study, we report that RILP, a downstream effector of Rab7, interacts with HOPS complex and recruits HOPS subu...

Phosphorylation of a membrane curvature–sensing motif switches function of the HOPS subunit Vps41 in membrane tethering

Tethering factors are organelle-specific multisubunit protein complexes that identify, along with Rab guanosine triphosphatases, transport vesicles and trigger their SNARE-mediated fusion of specific transport vesicles with the target membranes. Little is known about how tethering factors discriminate between different trafficking pathways, which may converge at the same organelle. In this pape...

How Vps41 HOPS between tethering functions

Cells find an alternative exit M ammalian cells can arrest and differentiate even in the complete absence of Rb family proteins, Wirt et al. reveal. The retinoblastoma (Rb) tumor suppressor and its close relatives p107 and p130 arrest cells in G1 by binding and inactivating E2F transcription factors, blocking transcription of E2F target genes required for cell cycle progression. The Rb family i...

Abnormal cerebellar development and ataxia in CARP VIII morphant zebrafish.

Congenital ataxia and mental retardation are mainly caused by variations in the genes that affect brain development. Recent reports have shown that mutations in the CA8 gene are associated with mental retardation and ataxia in humans and ataxia in mice. The gene product, carbonic anhydrase-related protein VIII (CARP VIII), is predominantly present in cerebellar Purkinje cells, where it interact...

TITLE: VPS18 recruits VPS41 to the human HOPS complex via a RING-RING interaction