Figure 7. Schematic diagram illustrating the involvement of the HDAC6-septin association in microtubule deacetylation and axon/dendrite growth.

HDAC6 is the major microtubule deacetylase, which promotes microtubule remodelling by counteracting acetyl transferases that stabilize microtubules55. This study demonstrated that the direct interaction with the septin complex facilitates the access of HDAC6 to acetylated α-tubulin and/or stabilizes the enzyme-substrate interaction without altering the deacetylation activity of HDAC6. An open question is whether the putative tripartite interaction of the septin complex/HDAC6/acetylated α-tubulin (a subset of the signals in the PLA assay shown in Fig. 5f should represent this) occurs on α/β-tubulin heterodimers, protofilaments and/or microtubules. It is also worth testing whether an actomyosin-dependent mechanism, including another HDAC6 substrate cortactin16, could contribute to the stagnant neurite growth after septin depletion. Independent of the specific underlying mechanism, the novel molecular network identified in this study has shed new light on the common machinery for the growth of axons and dendrites in vivo and in vitro.