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 midgut of Aedes aegypti females. The first phase, which encompasses the first 4-6 hours following a blood meal, is characterized by the presence of small amounts of early trypsin. The second phase, which occurs between 8 and 36 hours after blood feeding, is characterized by the presence of large amounts of late trypsin. A specific form of regulation of trypsin synthesis characterizes each phase: early trypsin synthesis is regulated at the translational level, while late trypsin synthesis is regulated at the transcriptional 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 "sensor". It carries out limited proteolysis of the ingested proteins and, somehow, the products of this limited proteolysis induce synthesis of late trypsin, which is the protease responsible for the majority of the endoproteolytic cleavage of the meal proteins. Transcription of the early trypsin gene starts a few hours after adult emergence and is under control of juvenile hormone. However, the early trypsin mRNA is stored in the midgut epithelium and remains untranslated until a blood meal is taken. The exact mechanism responsible for initiating translation 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 transcription of the late trypsin gene is proportional to the amount of protein present in the meal. In addition, the amount of late trypsin protein translation is controlled by the amount of amino acid released during digestion. Regulation at both transcriptional and translational levels allows the midgut to adjust the amount of late trypsin with remarkable flexibility in response to a particular meal.