| This body of work concerns the identification of a novel immunoglobulin-domain protein present at synapses throughout the mammalian brain, the delineation of its spatial and temporal expression pattern therein, and the discovery that it is subject to internal proteolytic cleavage by a mechanism not previously described in eukaryotic cells.; Immunoglobulin Superfamily Protein 1 (IgSF-1) was identified by an expression screen (Diaz et al.) to be present in the brain and to be upregulated during the developmental period of most intense synaptogenesis.; The present work examines the brain expression pattern of IgSF-1, and finds it to be ubiquitous in the brain and highly enriched at synapses. In addition, it is shown that IgSF-1, translated as a protein of eleven immunoglobulin (Ig) domains, is subject to sequential proteolytic cleavages by signal peptidase and signal peptide peptidase. This results in the generation of two smaller proteins of five and six Ig domains respectively, which show different patterns of subcellular and gross expression. To my knowledge, this constitutes the first demonstration of an internal cleavage event by signal peptidase and signal peptide peptidase in a eukaryotic protein.; These data demonstrate a novel role for signal peptidase and signal peptide peptidase in the mammalian brain, and introduce a new player at the mammalian central synapse. |
