However, crosssubfamily tetramerization is possible without the T1 domain since subunits lacking the T1 domain can also assemble into electrically functional channels at the PM, albeit less efficiently. For example, deletion of the N-terminal domain of the subunits resulted in the loss of subfamily-restricted coassembly of those subunits. Even though members of the subfamilies possess all the typical hallmarks of a Kv a-subunit, they do not form electrically functional homotetrameric channels at the PM. This is due to the retention of these ����silent���� subunits in the endoplasmic reticulum. The KvS subunits change the current density, shift the voltage dependence of activation and SR 27417 inactivation, change the gating kinetics and/or alter the pharmacological properties, as compared to homotetrameric Kv2 channels. In addition to the Kv2/KvS interaction, several KvS subunits have been suggested to interact with members of the Kv3 subfamily as well. Furthermore, yeast-two-hybrid analysis revealed an interaction of the subunits with the Nterminus of Kv3.1. However, there is no evidence of channels at the PM. This suggests that the subfamily-specific assembly of subunits into electrically functional channels. Our results indicate that the subfamily-specific tetramerization requires specific interactions. Phosphorylation/dephosphorylation of the neuronal microtubule associated protein Tau regulates in a complex manner its Clonixin capacity to assemble tubulin into microtubules. It is also associated with the presence of pathological fibrils in neurons of patients, which are mainly composed of hyperphosphorylated Tau. Monoclonal antibodies such as AT180 and AT8, recognizing respectively the pT231 phospho-motifs, are available for post-mortem diagnostics of the disease progression, and can define the neurofibrillary lesions at different stages of the disease. The spatial hierarchy observed is equally accompanied by a temporal progression of the phosphorylation pattern of Tau. The T231 site, for example, becomes phosphorylated early in the disease, and precedes phosphorylation. The phosphorylation of Tau is a reversible process, which implies that the pathological hyperphosphorylation can result from a deregulation of kinase and/or phosphatase activity.