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Definition
Trypsin-modulating oostatic factor (TMOF), a mosquito decapeptide, terminates trypsin biosynthesis in the mosquito gut. The hormone is secreted from the ovary, starting 18 hrs after the blood meal, circulates in the hemolymph, binds to a gut receptor and stops trypsin biosynthesis by exerting a translational control on trypsin mRNA 1.

Related Peptides
TMOF belongs to the family of Antigonadotrophins, or factors that inhibit egg development (oostatic hormones) 1.

Discovery
Borovsky (1985) reported that the mosquito ovary is a rich source of ‘oostatic hormone’. Injections of the hormone into female mosquitoes inhibited yolk deposition and vitellogenin biosynthesis. The hormone did not block the release of EDNH from mosquito brain and, thus, it was assumed that the hormone acted directly on the ovary, either by preventing pinocytosis or by inhibiting ecdysteroid biosynthesis. Even though the target tissue of the hormone is the mosquito midgut and not the ovary or the brain, the hormone was named TMOF 1.

Structural Characteristics
Borovsky and co-workers purified, sequenced and, using mass spectrometry, characterized the hormone as an unblocked decapeptide (NH2-YDPAPPPPPP-COOH). Several peptide analogues were synthesized and shown to possess TMOF activity .Because of the unique primary amino acid sequence of the hormone and its stable three-dimensional conformation, TMOF is not degraded by gut proteolytic enzymes and can traverse the gut epithelial cells into the hemolymph of adults and larvae. Using this unique property, hormone fed to different species of mosquito larvae stops food digestion and causes larval mortality. To determine the shortest amino acid sequence that can bind to the gut receptor and still cause high larval mortality, 25 analogues of TMOF were synthesized and tested. The tetrapeptide (YDPA) was as effective as the deca- peptide, indicating that the binding to the gut receptor is at the N-terminus of the molecule 1.

Mode of Action
TMOF does not act as a classical trypsin inhibitor [e.g. TLCK (p-tosyl-L-lysine chloromethyl ketone hydrochloride), TPCK (p-tosyl-L-phenylalanine chloromethyl ketone) and soybean trypsin inhibitor] that binds to the active site of serine proteases and prevents protein hydrolysis. TMOF binds to a specific gut epithelial cell receptor and then stops trypsin biosynthesis 1.

Functions
TMOF can be used as a new biorational insecticide against mosquito larvae 1. Neb-TMOF, the trypsin modulating oostatic factor of gray fleshfly Neobellieria bullata, is a hexapeptide with the following sequence: H-Asn-Pro-Thr-Asn-Leu-His-OH. It has been isolated from vitellogenic ovaries in 1994. TMOF, the newly discovered insect peptide, inhibits trypsin biosynthesis in the gut, lowers yolk polypeptide concentration in the hemolymph and strongly inhibits ecdysone biosynthesis by larval ring glands 2. Expressing TMV-TMOF in plants can be used as a general method to protect them against agricultural insect pests and to control vector mosquitoes 3.

References

1.     Borovsky D (2003). Trypsin-modulating oostatic factor: a potential new larvicide for mosquito control. The Journal of Experimental Biology., 206:3869-3875.

2.     Konopifiska D, Bartosz-Bechowski H, Kuczer M, Rosifiski G, Janssen I, DeLoof A (1998). Insect trypsin modulating oostatic factor (Neb-TMOF) and its analogs:Preliminary structure/biological function relationship studies. Letters in Peptide Science, 5:391-393.

3.     Borovsky D, Rabindran S, Dawson WO, Powell CA, Iannotti DA, Morris TJ, Shabanowitz J, Hunt DF, DeBondt HL, DeLoof A (2006). Expression of Aedes trypsin-modulating oostatic factor on the virion of TMV: A potential larvicide. PNAS., 103(50):18963-18968.

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