The multiple personalities of Alix

Abstract

Alix is a cytosolic protein in mammalian cells that was originally identified on the basis of its association with proapoptotic 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.

A Sleeping Beauty transposon-mediated screen identifies murine susceptibility genes for adenomatous polyposis coli ( Apc )-dependent intestinal tumorigenesis

“…Another gene identified in this study, Pdcd6ip (also known as ALG-2 interacting protein X, Alix) is involved in membrane trafficking and apoptosis (39). Pdcd6ip produces a protein that binds to the protein product of Pdcd6, a proapoptotic gene involved in T-cell receptor-, Fas-, and glucocorticoid-induced cell death (40).…”

Exosomes in colorectal carcinoma formation: ALIX under the magnifying glass

“…We found morphological and size similarity between the expression pattern of ALIX (in our adenoma and colorectal carcinoma samples) with TSG101 (involved in MVB and exosome formation, an interaction partner of ALIX) and CD63 molecules in in vitro and in vivo models of others. [55][56][57][58] Based on the relatively large (approximately 0.6-2 μm) diameter (knowing the inaccuracy deriving from fluorescent measurement) 59 and molecular composition of these particles they may designate MVBs including intracytoplasmic clusters of exosomes. These structures were also detectable on cancer-stroma border and adjacent carcinoma cells, which suggest that they have a role in cell-cell communication via elevated exosomal function.…”

Alix Protein Is Substrate of Ozz-E3 Ligase and Modulates Actin Remodeling in Skeletal Muscle

“…Alix is an evolutionary conserved, ubiquitously expressed adaptor protein that has been implicated in many cellular processes, including membrane and cytoskeleton remodeling (12). In fact, Alix has been shown to associate with F-actin in epithelial cells and fibroblasts, where it participates in the organization of actin fibers (14).…”

“…More recent reports have implicated Alix in other basic cellular processes, which all hinge on membrane trafficking, endosomal sorting, and remodeling of the actin cytoskeleton (12)(13)(14). These multitasking properties of Alix derive from the ability of the protein to interact with a plethora of partner proteins, which are themselves components of large oligomeric complexes.…”