Microtubule deacetylases, SirT2 and HDAC6, in the nervous system

Examination of the cytoskeleton has demonstrated the pivotal role of regulatory proteins governing cytoskeletal dynamics. Most work has focused on cell cycle and cell migration regarding cancer. However, these studies have yielded tremendous insight for development, particularly in the nervous system where all major cell types remodel their shape, generate unsurpassed quantities of membranes and extend cellular processes to communicate, and regulate the activities of other cells. Herein, we analyze two microtubule regulatory alpha-tubulin deacetylases, histone deacetylase-6 (HDAC6) and SirT2. HDAC6 is expressed by most neurons but is abundant in cerebellar Purkinje cells. In contrast, SirT2 is targeted to myelin sheaths. Expression of these proteins by post-mitotic cells indicates novel functions, such as process outgrowth and membrane remodeling. In oligodendrocytes, targeting of SirT2 to paranodes coincides with the presence of the microtubule-destabilizing protein stathmin-1 during early myelinogenesis and suggests the existence of a microtubule regulatory network that modulates cytoskeletal dynamics.