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: 5.43). 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.

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    • "In one particular study, the tumor marker extracellular matrix metalloproteinase inducer EMMPRIN [76] [77] was identified on SKBR3 and MCF-7 breast cancer-derived MVs, but not on exosomes [78]. On the other hand, the tetraspanin CD63, a binding partner of integrins and tumor marker whose expression inversely correlates with cancer metastasis [71, 79– 84], and tumor susceptibility gene 101 (TSG101), which is a subunit of the endosomal sorting complex required for transport-1 (ESCRT-1) [85], were present almost exclusively on exosomes [78]. Others have reported CD63, ALG-2- interacting protein X (Alix), which is involved in exosome biogenesis and endosomal sorting [86] [87], and TSG101, or a combination of these proteins, from MDA-MB-231, MCF- 7, T47D:A18, and Hs-578T breast cancer-derived exosomes [37] [45] [49] [50]. "
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    • "These proteins are composed of three main domains . A Bro1 domain in the N - terminal region , a proline - rich domain in the C - terminal region ( except for Rim20 ) , and connecting both domains , a relatively uncharacterized sequence containing one or two coiled - coil domains ( Odorizzi , 2006 ) ( Figure 2 ) . Similar domain composition was found in At - ALIX , which is predicted to contain two coiled - coil domains . "
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    • "These proteins are composed of three main domains . A Bro1 domain in the N - terminal region , a proline - rich domain in the C - terminal region ( except for Rim20 ) , and connecting both domains , a relatively uncharacterized sequence containing one or two coiled - coil domains ( Odorizzi , 2006 ) ( Figure 2 ) . Similar domain composition was found in At - ALIX , which is predicted to contain two coiled - coil domains . "
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