A molecular view of trypsin synthesis in the midgut of Aedes aegypti

Ingestion of a blood meal induces two phases of trypsin synthesis in the mi dgut of Aedes aegypti females. The first phase, which encompasses the first 4-6 hours following a blood meal, is characterized by the presence of smal l amounts of early trypsin. The second phase, which occurs between 8 and 36 hours after blood feeding, is characterized by the presence of large amoun ts of late trypsin. A specific form of regulation of trypsin synthesis char acterizes each phase: early trypsin synthesis is regulated at the translati onal level, while late trypsin synthesis is regulated at the transcriptiona l level. The enzymatic activity of early trypsin plays a unique and critical role in the regulation of late trypsin synthesis. Early trypsin acts like a "senso r". It carries out limited proteolysis of the ingested proteins and, someho w, the products of this limited proteolysis induce synthesis of late trypsi n, which is the protease responsible for the majority of the endoproteolyti c cleavage of the meal proteins. Transcription of the early trypsin gene starts a few hours after adult emer gence and is under control of juvenile hormone. However, the early trypsin mRNA is stood in the midgut epithelium and remains untranslated until a blo od meal is taken. The exact mechanism responsible for initiating translatio n is presently unknown, but an increase in the size of the amino acid pool in the midgut is sufficient to activate translation of early trypsin mRNA. The transcription of the late trypsin gene is regulated by uncharacterized proteolysis products generated by the action of early trypsin on the blood meal proteins. Once transcription has been activated, the rate of transcrip tion of the late trypsin gene is proportional to the amount of protein pres ent in the meal. In addition, the amount of late trypsin protein translatio n is controlled by the amount of amino acid released during digestion. Regu lation at both transcriptional and translational levels allows the midgut t o adjust the amount of late trypsin with remarkable flexibility in response to a particular meal. (C) 1999 Elsevier Science Ltd. All rights reserved.