A novel function of karyopherin beta 3 associated with apolipoprotein A-I secretion

Abstract

Human karyopherin beta 3, highly homologous to a yeast protein secretion enhancer (PSE1), has often been reported to be associated with a mediator of a nucleocytoplasmic transport pathway. Previously, we showed that karyopherin beta 3 complemented the PSE1 and KAP123 double mutant. Our research suggested that karyopherin beta 3 has an evolutionary function similar to that of yeast PSE1 and/or KAP 123. In this study, we performed yeast two-hybrid screening to find a protein which would interact with karyopherin beta 3 and identified apolipoprotein A-I (apo A-I), a secretion protein with a primary function in cholesterol transport. By using in vitro binding assay, coimmunoprecipitation, and colocalization studies, we defined an interaction between karyopherin beta 3 and apo A-I. In addition, overexpression of karyopherin beta 3 significantly increased apo A-I secretion. These results suggest that karyopherin beta 3 plays a crucial role in apo A-I secretion. These findings may be relevant to the study of a novel function of karyopherin beta 3 and coronary artery diseases associated with apo A-I.