Fig. 1

Schematic representation of effects of GFP label in preventing templated assembly of Tau^RD. (a) Self-assembly of Tau: Tau protein is highly hydrophilic and natively unfolded. In disease conditions, Tau becomes misfolded, attains β-structure and assembles into paired helical filaments. (b) Seeded (templated) assembly: Tau protein subunits elongate into long filaments using external Tau seeds as template (usually prepared by sonication of preformed fibrils). Note: In Tau assembly experiments in vitro, polyanions such as heparin must be added to initiate nucleation. (c)Pre-dominant hypothesis: In cell culture, Tau seeds (made from Tau^FL or Tau^RD) are internalized into acceptor cells. Endogenous Tau^RD is thought to attain the amyloid structure of the seeds and elongate the filaments. (d) Experimental observation: In cell culture studies Tau^RD-GFP is often used as endogenous Tau fusion protein, intended to elongate templating seed structures. However, steric hindrance by the large GFP molecule prevents fiber formation