TLN was identified from a yeast two-hybrid screen of a mouse hippocampus library using a C-terminal fragment of PS1 as bait. The group subsequently separated TLN from brain extracts using an immobilized PS1 C-terminal fragment. Surprisingly, the reverse experiment, using an immobilized fragment of the TLN transmembrane domain, separated both C-terminal and N-terminal fragments of PS1, indicating that both ends of the protein bind to TLN. PS1's TLN-binding sites are amino acids 1-163, which cover the first transmembrane domain, and the 39 C-terminal residues, which are predicted to lie in the cytosol. These findings suggest that, in vivo, the PS1 molecule may form a ring structure, with the C- and N-terminals coming into contact with TLN. In addition, the same PS1 sites were found to bind to AβPP, suggesting a common mode of interaction between presenilins and their molecular partners.

"Though telencephalin, which is localized in the telencephalon and is not a PS substrate, is not directly involved in Alzheimer's disease, this data may be functionally important in understanding how presenilins work," commented Christian Haass, Ludwig-Maximilians University, Munich. "The ring structure is almost certainly correct, though proving this directly in vivo will be difficult."-Tom Fagan.

Reference:Annaert WG, Esselens C, Baert V, Boeve C, Snellings G, Cupers P, Craessaerts K, De Strooper B. Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins. Neuron 20 November 2001;(32):579-589. Abstract