Article

The multiple personalities of Alix

Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
Journal of Cell Science (Impact Factor: 5.33). 09/2006; 119(Pt 15):3025-32. DOI: 10.1242/jcs.03072
Source: PubMed

ABSTRACT Alix is a cytosolic protein in mammalian cells that was originally identified on the basis of its association with pro-apoptotic signaling. More recent evidence has established that Alix has a hand in regulating other cellular mechanisms, including endocytic membrane trafficking and cell adhesion. Although Alix appears to participate directly in these various activities, the role it plays in each process has largely been inferred from the functions of proteins with which it interacts. For example, recruitment of Alix to endosomes is mediated by its N-terminal Bro1 domain, the structure of which was recently solved for its yeast orthologue, Bro1. The diversity of Alix functions is due to its proline-rich C-terminus, which provides multiple protein-binding sites. With this blueprint in hand, we can now ask whether Alix acts simply as an adaptor that links different proteins into networks or, instead, contributes a specific function to distinct molecular machineries.

0 Bookmarks
 · 
68 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Male reproductive glands secrete signals into seminal fluid to facilitate reproductive success. In Drosophila melanogaster, these signals are generated by a variety of seminal peptides, many produced by the accessory glands (AGs). One epithelial cell type in the adult male AGs, the secondary cell (SC), grows selectively in response to bone morphogenetic protein (BMP) signaling. This signaling is involved in blocking the rapid remating of mated females, which contributes to the reproductive advantage of the first male to mate. In this paper, we show that SCs secrete exosomes, membrane-bound vesicles generated inside late endosomal multivesicular bodies (MVBs). After mating, exosomes fuse with sperm (as also seen in vitro for human prostate-derived exosomes and sperm) and interact with female reproductive tract epithelia. Exosome release was required to inhibit female remating behavior, suggesting that exosomes are downstream effectors of BMP signaling. Indeed, when BMP signaling was reduced in SCs, vesicles were still formed in MVBs but not secreted as exosomes. These results demonstrate a new function for the MVB-exosome pathway in the reproductive tract that appears to be conserved across evolution.
    The Journal of Cell Biology 08/2014; 206(5). DOI:10.1083/jcb.201401072 · 9.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: GAIP interacting protein C terminus (GIPC) is known to play an important role in a variety of physiological and disease states. In the present study, we have identified a novel role for GIPC as a master regulator of autophagy and the exocytotic pathways in cancer. We show that depletion of GIPC-induced autophagy in pancreatic cancer cells, as evident from the upregulation of the autophagy marker LC3II. We further report that GIPC regulates cellular trafficking pathways by modulating the secretion, biogenesis, and molecular composition of exosomes. We also identified the involvement of GIPC on metabolic stress pathways regulating autophagy and microvesicular shedding, and observed that GIPC status determines the loading of cellular cargo in the exosome. Furthermore, we have shown the overexpression of the drug resistance gene ABCG2 in exosomes from GIPC-depleted pancreatic cancer cells. We also demonstrated that depletion of GIPC from cancer cells sensitized them to gemcitabine treatment, an avenue that can be explored as a potential therapeutic strategy to overcome drug resistance in cancer.
    PLoS ONE 12/2014; 9(12):e114409. DOI:10.1371/journal.pone.0114409 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Exosomes are nanosized vesicles secreted by cells, which are capable of carrying signaling molecules in the forms of protein, mRNA and miRNA to serve as the platforms for complex intercellular communications. During the past few years, increasing efforts have been devoted to exosome research, and tremendous progress has been made in terms of identifying the molecular composition, elucidating the mechanisms and regulations of biogenesis and characterizing the functions in a variety of physiological and pathological settings including cardiovascular diseases, a leading cause of morbidity and mortality in modern society. This review provides an update on exosome research and summarizes the roles of exosomes in cardiovascular diseases.
    Heart Failure Reviews 12/2014; DOI:10.1007/s10741-014-9469-0 · 3.99 Impact Factor

Preview

Download
0 Downloads
Available from