Presenilin I interaction with cytoskeleton and association with actin filaments

Presenilin I (PSI) has been shown to interact with microfilament-associated proteins of the filamin family. Here, we investigated a possible association of PSI with the cytoskeleton. Immunoblotting of detergent-insoluble fractions of rat brain homogenate revealed enrichment of neuron-specific 36 and 14 kDa proteolytic fragments of PSI, whereas 30 and 20 kDa fragments were found in the detergent-soluble fraction. Specific severing of microfilaments with gelsolin in the detergent- insoluble pellet and subsequent centrifugation led to the detection of both actin and PSI fragments in the supernatant. In addition, in vitro translated PSI cosedimented with actin filaments. Our findings provide biochemical evidence for the association of PSI fragments with actin filaments.