Drosophila sequences

Details Drosophila sequences Drosophila sequences

1999-03-17

2004-03-09

Horlick, Kenneth R. (Department: 1637)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

C435S006120, C435S252300, C435S320100

Reexamination Certificate

active

06703491

ABSTRACT:

1. INTRODUCTION
The present invention relates to Drosophila genes and methods for their use. The invention provides nucleotide sequences of Drosophila genes, amino acid sequences of the encoded proteins, and derivatives (e.g., fragments) and analogs thereof. The invention further relates to fragments (and derivatives and analogs thereof) of proteins which comprise one or more domains of a Drosophila protein. Antibodies to Drosophila proteins, and derivatives and analogs thereof, are also provided. Also provided herein are vectors and host cells comprising such nucleic acids. Methods of production of a Drosophila protein (e.g., by recombinant means), and derivatives and analogs thereof, are provided. Chimeric polypeptide molecules comprising polypeptides of the invention fused to heterologous polypeptide sequences are provided. Methods to identify the biological function of a Drosophila gene are provided, including various methods for the functional modification (e.g., overexpression, underexpression, mutation, knock-out) of one gene, or of two or more genes simultaneously. Methods to identify a Drosophila gene which modifies the function of, and/or functions in a downstream pathway from, another gene are provided. The invention further provides for use of Drosophila proteins as media additives or pesticides.
2. BACKGROUND OF THE INVENTION
Citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.
2.1. G-Protein Coupled Receptors
G-protein coupled receptors (GPCRs) form an extensive family of transmembrane regulatory proteins that elicit intracellular signals in nearly every physiological system of chordates and invertebrate organisms. As a consequence of relatively small ligand-binding sites and the wide range of physiological events which they regulate, GPCRs have established the precedent of being the largest class of drug targets in humans. As described below, the sequence conservation of GPCRs across vertebrate and invertebrate species suggests that novel receptors identified in invertebrate species could aid in identification of homologues in other species, and the application of the appropriate agonist or antagonist mammalian receptor drugs to invertebrate species could result in the identification of effective pesticide agents. GPCRs can be divided into five broad structural classes, A-E, based on amino acid sequence similarity and sequence motifs. The largest class is class A, which can, in turn, be divided into subgroups according to receptor sequence similarity and ligand characteristics. The categorization of these relationships is illustrated by the following examples:
Class A (rhodopsin-like) GPCRs include: biogenic amine receptors (e.g. &agr;-adrenergic, &bgr;-adrenergic, dopamine, histamine, muscarinic acetylcholine, melatonin, 5-HT, octopamine and tyramine); peptidic ligand receptors (e.g., angiotensin, bombesin, chemokine, endothelin, galanin, hormone protein, F-met-leu-phe, melanocortin, N-formyl peptide, neuropeptide Y, neurokinin, opiate, tachykinin, vasopressin, oxytocin and somatostatin); rhodopsin receptors (e.g., vertebrate rhodopsin, arthropod rhodopsin, and olfactory receptors); prostanoid receptors (e.g., prostaglandin, prostacyclin, and thromboxane); nucleotide receptors (e.g., adenosine and purinoceptors); hormone-releasing GPCRs (e.g., gonadotropin-releasing hormone, thyrotropin-releasing hormone, growth hormone, and secretagogue GPCRs);
Class B (secretin like) GPCRs include calcitonin, calcitonin releasing factor, calcitonin gene-related peptide, gastrin, cholecystokinin, glucagon, growth hormone-releasing hormone, parathyroid hormone, vasoactive intestinal peptide, PACAP, diuretic hormone and secretin GPCRs;
Class C (metabotropic glutamate-like) GPCRs include metabotropic glutamate, metabotropic GABA
B
, and extracellular calcium-sensing GPCRs;
Class D includes pheromone GPCRs; and
Class E includes cAMP-binding GPCRs.
Among their many functions, extensive study has revealed that GPCRs play a prominent role as receptors for neurotransmitters within the central and peripheral nervous systems, notably illustrated by the biogenic amine ligands such as norepinephrine (NE), octopamine (Oct), dopamine (DA), acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). Several GPCRs for the biogenic amines have been identified in insects by pharmacological and molecular cloning approaches, including two octopamine/tyramine receptors from
Drosophila melanogaster
(Arakawa et al., 1990, Neuron 4, 343-354; Saudou et al., 1990, EMBO 9, 3611-3617; Han et al., 1990, J. Neurosci. 18, 3650-3658; see also Venter et al, U.S. Pat. Nos. 5,474,898 and 5,344,776) as well from other insect species such as moth, locus, and honey bee (von Nickisch-Rosenegk et al., 1996, Insect Biochem. Mol. Biol. 26: 817-827; Hiripi et al., 1994, Brain Res. 7, 119-126; Roeder et al., 1995, Prog. Brain Res. 106, 249-258; Evans, 1987, J. Exp. Biol. 129:239-250; Ebert et al., 1998, Insect Mol. Biol. 7, 151-162). Two putative Drosophila dopamine receptors, (Sugamori et al., 1995, FEBS Lett. 362, 131-138; Feng et al., 1996, J. Neurosci. 16, 3925-3933), two 5-HT receptors (Saudou et al., 1992, EMBO J. 11, 7-17), and one muscarinic acetylcholine receptor (Shapiro et al., 1989, Proc. Natl. Acad. Sci. U.S.A. 86, 9039-9043) have been identified and molecularly cloned, and are shown to be expressed in the nervous system. Glutamate and GABA are also CNS neurotransmitters involved in memory and mediation of pain sensation, and the metabotropic glutamate and GABA GPCRs form a structurally separate class of receptors (Class C). A Drosophila metabotropic glutamate receptor has been cloned and is expressed in the embryonic central nervous system (CNS) (Parmentier et al., 1996, J. Neurosci. 16, 6687-6694).
Other classes of GPCRs, such as rhodopsins and odorant receptors, are light and chemosensory receptors for the CNS and enable the senses of vision and odor. A number of rhodopsin genes have been identified and sequenced from
Drosophila melanogaster, virilis
, and
simulans
(Carulli et al., 1994, J. Mol. Evol. 38, 250-262), honey bee (Bellingham et al., 1997, Eur. J. Biochem. 243, 775-781; Townson et al., 1998, J. Neurosci. 18, 2412-2422), ant and tobacco hornworm (Chase et al., 1997, J. Exp. Biol. 200, 2469-2478; Popp et al., 1996, Invert. Neurosci. 1, 323-329). Related to actions within the nervous system, GPCRs regulate aspects of neuroendocrine secretion such as thyroid releasing hormone (TRH), thyroid stimulating hormone (TSH), growth hormone releasing hormone (GHRH), adrenocorticotropin (ACTH), and water balance via diuretic hormone or vasopressin. Extending to the regulation of cell growth and mammalian reproduction, GPCRs can couple to mitogenic pathways as illustrated by the bombesin and endothelin receptors, and can control ovulation, lactation and birth through the action of follicular stimulating hormone (FSH), luteinizing hormone (LH), and oxytocin.
Numerous neuropeptides have been identified from insects which perform similar overall roles to some of these mammalian peptides. However, the molecular characterization is incomplete with respect to the insect GPCRs which bind these analogous peptides; several may be homologous to mammalian receptors. A number of diuretic peptides, including an arginine vasopressin-like diuretic hormone, have been identified in locusts (Lehmberg et al., 1991, Biochem. Biophys. Res. Comm. 179, 1036-1041; Thompson et al., 1995, Peptides 16, 95-104; Schoofs et al., 1997, Peptides 18, 145-156; Proux et al., 1987, Biochem. Biophys. Res. Comm. 149, 180-186), while a diuretic hormone GPCR has been cloned from the house cricket and tobacco hornworm (Reagan, 1996, Insect Biochem. Mol. Biol. 26, 1-6; Reagan, 1994, Biol. Chem. 269, 9-12). A Drosophila GPCR with 50% identity to the transmembrane regions of rat TSH, FSH, and LH receptors has been cloned and sequenced (Hauser et al., 1997, J. Biol. Chem. 272, 1002-1010). Within the immune system, GPCRs can influence neutrophil chemotaxis through the action of ch

Affiliated with

Also associated with

Rating

Drosophila sequences does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Drosophila sequences, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Drosophila sequences will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3228486