Role of synemin in astrocytoma cellmigration

Abstract

Synemin is an intermediate filament (IF) protein with the unique property to incorporate into IF networks while also binding to actin-associated proteins such as a-actinin, vinculin, zyxin, and a-dystrobrevin. Interestingly, synemin is present in astrocytomas of all grades but not in normal, mature astrocytes. Synemin contribution to the malignant behavior of astrocytoma cells was explored through RNAi experiments that established that synemin is a positive regulator of astrocytoma cell motility. In support of this role is the abundance of synemin in cytoplasmic domains important for motility, such as leading edges and lamellipodias. Synemin down-regulation also disrupted actin organization and increased the proportion of unpolymerized actin. In addition, antagonizing synemin decreased the proportion of a-actinin associated with actin filaments, providing evidence that synemin interaction with a-actinin may influence actin dynamics upon which motility ultimately depends. In addition to synemin, astrocytoma cells express two other IF proteins, vimentin and nestin. These latter two proteins contribute to the motility of carcinoma and/or fibroblastic cells, raising the possibility that they function similarly in astrocytoma cells. However, in contrast to synemin, vimentin and nestin are not present in the leading edge of astrocytoma cells, suggesting that they influence motility through mechanism(s) distinct from that of synemin. Thus, antagonizing synemin function appears to diminish the motility of astrocytoma cells and future studies will determine whether antagonizing synemin can be accomplished with small molecules such as those being developed to target other IF proteins.

Publication Title

Tumors of the Central Nervous System: Astrocytomas, Hemangioblastomas, and Gangliogliomas

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