Researchers from Bart de Strooper's lab at the Flanders Interuniversity Institute for Biotechnology, reported in the 20 November Neuron that telencephalin (TLN), a member of the intercellular adhesion molecule (ICAM) family, binds to presenilins 1 and 2 (PS1 and PS2), components of the amyloid precursor protein (AβPP) γ-secretase complex that is implicated in the etiology of Alzheimer's disease.

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


  1. Another function for ps, also related to protein degradation but not like app or notch clevage.

    View all comments by Edward Koo

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Primary Papers

  1. . Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins. Neuron. 2001 Nov 20;32(4):579-89. PubMed.