We examined the function of LIP5 in mammalian cells, because the yeast homologue Vta1p was recently identified as a protein required for multivesicular body (MVB) formation. LIP5 is predominantly a cytosolic protein. Depletion of LIP5 by small inhibitory RNA (siRNA) does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does reduce the degradation of internalized epidermal growth factor receptor (EGFR), with EGFR accumulating in intracellular vesicles. Depletion of LIP5 by siRNA also decreases human immunodeficiency virus type 1 (HIV-1) budding by 70%. We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR similar to silencing of LIP5. Surprisingly, CHMP5 depletion results in an increase in the release of infectious HIV-1 particles. Overexpression of CHMP5 with a large carboxyl-terminal epitope affects the distribution of both early and late endocytic compartments, whereas overexpression of LIP5 does not alter the endocytic pathway. Comparison of overexpression and siRNA phenotypes suggests that the roles of these proteins in MVB formation may be more specifically addressed using RNA interference and that both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release.Endosomes play a crucial role in transporting molecules from the plasma membrane to intracellular compartments as well as transporting molecules from the biosynthetic apparatus to their site of action (1-3). Several different endosomal compartments have been described based on morphology, constituents, and role within the endocytic apparatus. The multivesicular body (MVB) 1 is an endosomal compartment that serves to sort membrane proteins destined for degradation or routing to the lysosome (4 -6). These proteins are internalized into vesicles that form by the invagination of the limiting membrane (forming intravesicular vesicles). The contents of the MVB are then transferred to lysosomes. The physiologic importance of MVBs has been shown through studies in organisms as diverse as yeast and humans (5, 7-11). In yeast, the role of the MVB has been defined through the identification of mutations that alter protein sorting through the MVB (12). A specific class of sorting mutants, class E vacuolar protein sorting (VPS) mutations, results in the accumulation of transport cargo in a prevacuolar compartment and a selective deficit in the delivery of that cargo to vacuoles (7, 13-16). The class E phenotype is described as an enlarged late endosomal compartment, which presumably arises because of an inability to invaginate the limiting membrane that would normally form the MVB. In higher eukaryotes, studies on the internalization and degradation of growth factor receptors as well as studies on viral budding have helped to elucidate the importance of MVBs, because many enveloped RNA viruses utilize ...

We describe a new catalog of accelerating star candidates with Gaia G ≤ 17.5 mag and distances d ≤ 100 pc. Designated as the Gaia Nearby Accelerating Star Catalog (GNASC), it contains 29,684 members identified using a supervised machine-learning algorithm trained on the Hipparcos–Gaia Catalog of Accelerations (HGCA), Gaia Data Release 2, and Gaia Early Data Release 3. We take advantage of the difference in observation timelines between the two Gaia catalogs and information about the quality of the astrometric modeling based on the premise that acceleration will correlate with astrometric uncertainties. Catalog membership is based on whether constant proper motion over three decades can be ruled out at high confidence (greater than 99.9%). Test data suggest that catalog members each have a 68% likelihood of true astrometric acceleration; subsets of the catalog perform even better, with the likelihood exceeding 85%. We compare the GNASC with Gaia Data Release 3 and its table of stars for which acceleration is detected at high confidence based on precise astrometric fits. Our catalog, derived without this information, captures over 96% of the sources in the table that meet our selection criteria. In addition, the GNASC contains bright, nearby candidates that were not in the original Hipparcos survey, including members of known binary systems as well as stars with companions yet to be identified. It thus extends the HGCA and demonstrates the potential of the machine-learning approach for discovering hidden partners of nearby stars in future astrometric surveys.