HUMAN ERYTHROID SPECTRIN ALPHA-SUBUNIT AND ITS SH3 DOMAIN ARE SENSITIVE TO ACIDIC PLASMODIUM-FALCIPARUM PROTEOLYTIC ACTIVITY

Many proteases play a crucial role in the Plasmodium intraerythrocytic life cycle. Spectrin depletion, one of the major event involved in pa rasite release from the red blood cell, results from proteolytic activ ities associated with the presence of the intracellular parasite. Here , we describe a new acidic proteolytic activity from Plasmodium falcip arum, whose target is the alpha-subunit of human spectrin. Immunoblott ing experiments with antibodies specific for the tryptic peptides of t he alpha-chain, and in vitro proteolysis tests on recombinant peptides from different regions of the spectrin alpha subunit, demonstrated th at cleavage sites for the parasite proteolytic activity were localized within the SH3 motif of the alpha-chain sequence. Remarkably, this Pl asmodium protease activity on spectrin SH3 substrate was unable to cle ave the SH3 from fodrin, a non-erythroid spectrin.