Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Binds antigen or epitope whose amino acid sequence is...
Reexamination Certificate
1999-11-12
2003-09-23
Eyler, Yvonne (Department: 1646)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Binds antigen or epitope whose amino acid sequence is...
C424S141100, C424S148100, C424S154100, C424S172100, C424S145100, C435S007100, C435S332000, C530S387900
Reexamination Certificate
active
06623738
ABSTRACT:
FIELD OF THE INVENTION
The field of this invention is proteins involved in nerve cell guidance.
BACKGROUND
During nervous system development, axons migrate along prescribed pathways in the embryo to reach their appropriate synaptic targets (reviewed in Tessier-Lavigne and Goodman, 1996). One mechanism that contributes to accurate pathfinding is chemorepulsion, the guidance of axons away from non-target regions by diffusible chemorepellent factors secreted by non-target cells. Experiments in which axons are confronted with non-target tissues in tissue culture and are repelled by these tissues at a distance have demonstrated the existence of diffusible chemorepellent activities for numerous axonal classes (Pini, 1993; Fitzgerald et al., 1993; Colamarino and Tessier-Lavigne, 1995; Tamada et al., 1995; Guthrie and Pini, 1995; Shirasaki et al., 1996) as well as for migrating neuronal cells (Hu and Rutishauser, 1996). At the molecular level, two families of guidance cues, the netrin and semaphorin families, have been shown to comprise members that can function as chemorepellents. In Caenorhaditis elegans, the netrin UNC-6 is thought to repel axons that migrate away from the netrin source since these axons are misrouted at a certain frequency in unc-6 mutants; this presumed repulsion appears to be mediated by the candidate receptors UNC-5 and UNC-40, which are members of the immunoglobulin superfamily (Hedgecock et al., 1990; Leung-Hagesteijn et al, 1992; Hamelin et al., 1993; Wadsworth et al., 1996; Chan et al., 1996). Similarly, in vertebrates netrin-1 can repel subsets of motor axons that migrate away from a source of netrin-1 (Colamarino and Tessier-Lavigne, 1994; Varela-Echavarria et al., 1997), a process which might involve vertebrate homologues of UNC-5 and UNC-40, which have been shown to be netrin-binding proteins (Leonardo et al., 1997; Ackermann: et al., 1997; Keino-Masu et al., 1996).
The semaphorins are a large family of structurally diverse secreted and transmembrane proteins characterized by the presence of a conserved ~500 amino acid semaphorin domain at their amino termini (reviewed in Kolodkin, 1996). The family was first described and implicated in axon guidance through antibody perturbation studies in insects (Kolodkin et al., 1992; Kolodkin et al., 1993). The connection of this family to chemorepulsion was made with the purification of chicken collapsin-1 as a factor that can cause collapse of sensory growth cones when added acutely in cell culture (Luo et al., 1993). Collapsin-1 and its mammalian homologues (Semaphorin III, also known as Semaphorin D) are secreted semaphorins that possess in addition to the semaphorin domain an immunoglobulin domain and a highly basic carboxy-terminal domain (Luo et al., 1993; Kolodkin et al., 1993; Messersmith et al., 1995; Püschel et al., 1995). When presented chronically from a point source, collapsin-1/SemaIII/D (hereafter referred to as SemaIII) can repel sensory and sympathetic axons and has been implicated in patterning sensory axon projections into the ventral spinal cord (Messersmith et al., 1995; Püschel et al., 1995, 1996; Behar et al., 1996; Shepherd et al., 1997). Sema E, which is structurally-related to SemaIII, has also been reported to repel sympathetic axons in culture (cited in Varela-Echavarria and Guthrie, 1997). In Drosophila, the secreted semaphorin SemaII has been implicated as an inhibitor of axon terminal branch formation (Matthes et al., 1995). However, the mechanisms through which semaphorins produce their repellent or inhibitory actions have not been determined.
To elucidate the mechanisms through which semaphorin proteins produce their repulsive actions on axons, we have sought to identify binding proteins for semphorins on the surfaces of sensory axons. Here we identify two classes of semaphorin receptors, SR1 and SR2, expressed by axons whose function is required for the collapse-inducing and repulsive actions of semaphorins.
SUMMARY OF THE INVENTION
The invention provides methods and compositions relating to isolated semaphorin receptor class 1 and 2 (SR1 and SR2. collectively SR) polypeptides, related nucleic acids, polypeptide domains thereof having SR-specific structure and activity, and modulators of SR function, particularly semaphorin-binding activity. SR polypeptides can regulate cell, especially nerve cell, function and morphology. The polypeptides may be produced recombinantly from transformed host cells from the subject SR polypeptide encoding nucleic acids or purified from mammalian cells. The invention provides isolated SR hybridization probes and primers capable of specifically hybridizing with the disclosed SR genes, SR-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis (e.g. genetic hybridization screens for SR transcripts), therapy (e.g. SR inhibitors to promote nerve cell growth) and in the biopharmaceutical industry (e.g. as immunogens, reagents for isolating other Srs, reagents for screening chemical libraries for lead pharmacological agents, etc.).
REFERENCES:
Kawakami A. et al., Developmentally regulated Expression of a Cell Suface Protein, Neuropilin, in Mouse Nervous System, Jan. 1, 1996 Journal of Neurobiology, vol. 29, No. 1, p. 1-17.
He Z. et al., Neuropilin is a Receptor for the Axonal Chemorepellent Semaphorin II. 1997 Cell, vol. 90, p. 739-751.
Kolodkin A. et al., Neuropilin is a Semaphorin III Receptor, 1997 Cell, vol. 90 p. 753-762.
Takagi S. et al., Expression of a Cell Adhesion Molecule, Neuropilin, in the Developing Chick Nervous system, 1995 Developmental Biology, vol. 170, p. 207-222.
Takagi S. et al., The A5 Antigen, a candidate for the Neuronal Recognition Molecule, has Homologies to Complement Components and Coagulation Factors, 1991 Neuron, vol. 7, p. 295-307.
Chen, H. et al., Neuropilin-2, a Novel member of the Neuropilin family, is a high affinity receptor for the Semaphorins Sema E and Sema IV but not Sema III, Sep. 1997 Neuron, vol. 19, p. 547-559.
Pharmagenics Inc., 1993 ID Q31949 standard, DNA, 405 bp, Accession No. Q31949, N-geneseq 32 Database.
Harvard College, 1994 ID R51427 standard, Protein, 33 AA, Accession No. R51726, A-geneseq32 Database.
Hoeschst Japan Ltd., 1994 ID R49994 standard, 1128 AA, Accession No. R49994, A-geneseq32 Database.
Weissenbach, J. et al., 1994 HS24XB10, H. sapiens (D5S429) DNA Segment containing (CA) repeat; Clone AFM24xb10, Accession No. Z17097 emb156 Database.
Hillier, L. et al., 1995 H99253 497 bp mRNA, yx21h06.s1 Homo sapiens cDNA 262427 3′, human clone 26247, Accession No. H99253, embl-est56 Database.
Chen Hang
He Zhigang
Tessier-Lavigne Marc
Basi Nirmal S.
Eyler Yvonne
Osman Richard Aron
The Regents of the University of California
LandOfFree
Semaphorin receptors does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Semaphorin receptors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Semaphorin receptors will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3018904