The Tsc1-Tsc2 complex influences neuronal polarity by modulating TORC1 activity and SAD levels

Abstract

Neuronal function depends on the specification of neuronal processes as axons or dendrites. In this issue of Genes & Development Choi and colleagues (2485-2495) show that without Tuberous Sclerosis Complex 1 (Tsc1) or Tsc2, molecules linked to the autosomal dominant disease tuberous sclerosis, an increase in the activity of the translational regulator Target of Rapamycin 1 (TORC1) causes neurons to have multiple axons and the translation of SAD kinase increases as well. Thus, in addition to the kinase LKB1, the Tsc1-Tsc2 complex, acting through TORC1, also modulates SAD to regulate axon formation.

Figure 1.

Two pathways that promote axon formation by regulating SAD activity or SAD protein levels. Prior studies revealed that SAD activity is positively regulated by LKB1, which is activated in response to extracellular signals such as BDNF (Barnes et al. 2007; Shelly et al. 2007). In a new report published in this issue of Genes & Development, Choi et al. (2008) present evidence for a parallel pathway, regulated by the Tsc1–Tsc2 complex and TORC1, which modulates SAD protein levels. This new work suggests that local protein synthesis in the nascent axon is critical for neurons to polarize.