1 NgR1 and FGF receptor 1 (FGFR1) are colocalized to synap
2 NgR1 and PlexinA2 also interact genetically in vivo to r
3 NgR1 expression by parvalbumin expressing interneurons i
4 NgR1 gene deletion enhances anatomical changes of inhibi
5 NgR1 is the founding member of the three-member NgR fami
6 NgR1, an axonal glycoprotein, is the founding member of
7 NgR1, but not NgR3, forms a receptor complex with Plexin
8 receptor/p75 neurotrophin receptor/LINGO-
1 (
NgR1/p75/LINGO-1) complex.
9 icity inhibitors Nogo-A and Nogo receptor
1 (
NgR1) are differentially expressed in the SVZ-OB system,
10 Nogo-66 receptor
1 (
NgR1) binds a variety of structurally dissimilar ligands
11 e that Nogo-A activation of Nogo-receptor
1 (
NgR1) can drive axonal dystrophy during the neurological
12 Neuronal Nogo-66 receptor
1 (
NgR1) has been proposed to function as an obligatory cor
13 We examined whether Nogo Receptor
1 (
NgR1) regulates the plasticity associated with fear exti
14 oke is in part mediated via Nogo receptor
1 (
NgR1) signaling.
15 Nogo-66 receptor
1 (
NgR1) supports binding of the myelin inhibitors Nogo-A,
16 ted the CST in mice lacking nogo receptor
1 (
NgR1), a protein implicated in limiting neural repair.
17 lar prion protein (PrP(C)), Nogo receptor
1 (
NgR1), and leukocyte immunoglobulin-like receptor subfam
18 complex, composed of the Nogo-66 receptor
1 (
NgR1), neurotrophin p75 receptor (p75), and LINGO-1, rep
19 teract with the neuronal Nogo-66 receptor
1 (
NgR1).
20 n molecule A (JAM-A) and Nogo-66 receptor
1 (
NgR1).
21 ing as ligands for neuronal Nogo receptor
1 (
NgR1).
22 sory cortex of mice lacking Nogo Receptor
1 (
NgR1).
23 -dependent manner to the Nogo-66 receptor-
1 (
NgR1) and its homolog NgR2.
24 onal cell surface receptors Nogo receptor-
1 (
NgR1) and paired Ig-like receptor-B (PirB) to regulate n
25 ce (LOTUS) as an endogenous Nogo receptor-
1 (
NgR1) antagonist and demonstrated that LOTUS contributes
26 Neuronal Nogo66 receptor-
1 (
NgR1) binds the myelin inhibitors NogoA, OMgp, and myeli
27 e sigma (RPTPsigma), and Nogo receptors 1-
3 (
NgR1-3).
28 harmacological experiments show that Nogo-
66/
NgR1 interaction reduces the proliferation of NSCs.
29 cal axon regeneration by Nogo-A depends on
a NgR1/PlexinA2 genetic interaction because double-heteroz
30 Thus,
a NgR1/PlexinA2/CRMP2 ternary complex limits neural repair
31 ss 3 Semaphorins, with or without
additional NgR1 deletion.
32 g antibodies (Abs) against Nogo-A or
against NgR1 increased long-term potentiation (LTP) induced by s
33 led that Nogo-66 and OMgp suppress LTP in
an NgR1-dependent manner.
34 A Nogo signaling blockade with
an NgR1 antagonist administered after stroke reduces the OP
35 Cellular signaling by lipid-
anchored NgR1 requires a coreceptor but the relevant partner in v
36 A physiologic role for Nogo-A
and NgR1 has been documented in the restriction of experienc
37 a new unprecedented function for Nogo-A
and NgR1 in the homeostatic regulation of the pace of neurog
38 We therefore examined the role of Nogo-A
and NgR1 in the regulation of neurogenesis.
39 These findings suggest that Nogo-A
and NgR1 interactions may contribute to axonal branching in
40 Further analysis of the Nogo-A
and NgR1 interactions revealed a novel third interaction sit
41 Reovirus virions bind to soluble JAM-A
and NgR1, while infectious disassembly intermediates (ISVPs)
42 We propose that MT3-MMP activity
and NgR1 shedding could stimulate circuitry remodeling in th
43 Both PrP(C)
and NgR1 preferentially bound synaptotoxic oligomers rather
44 s rescued in the double mutant of LOTUS-
and NgR1-KO mice.
45 PirB(-/-) and NgR1(-/-) single mutants
and NgR1(-/-);PirB(-/-) double mutants show normal LTP, indi
46 h Nogo-A identifies immature neuroblasts
and NgR1 germinal astrocytes.
47 PirB(-/-)
and NgR1(-/-) single mutants and NgR1(-/-);PirB(-/-) double
48 ation routes, also were comparable in WT
and NgR1(-/-) mice, suggesting that NgR1 is dispensable for
49 eplication and disease in wild-type (WT)
and NgR1(-/-) mice.
50 ion and detailed characterization of an
anti-
NgR1 monoclonal antibody, 7E11.
51 Thus, specific
anti-
NgR1 antibodies may represent a useful therapeutic appro
52 Our data demonstrate that
anti-
NgR1 antibodies recognizing this epitope, such as 7E11,
53 ling by interfering with interaction
between NgR1 and its coreceptors p75NTR or LINGO-1.
54 re, we report on a novel interaction
between NgR1 and select members of the fibroblast growth factor
55 wledge of the molecular interactions
between NgR1 and its ligands is imperative when assessing option
56 em-specific transmembrane protein that
binds NgR1 and p75 and that is an additional functional compon
57 Blocking NgR1 on transfected cells or primary cortical neurons ab
58 Non-neuronal cells expressing
both NgR1 and PlexinA2, but not either protein alone, contrac
59 Hippocampal neurons lacking
both NgR1 and LilrB2 exhibited a partial reduction of Abetao
60 ment of the chicken spinal cord in vivo
Both NgR1 and NgR3 are required for midline crossing and subs
61 In postnatal
brain NgR1 and NgR2 are strongly enriched in Triton X-100-inso
62 Suppression of anatomical dynamics
by NgR1 is cell autonomous and is phenocopied by deletion o
63 n growth inhibition by myelin is mediated
by NgR1-independent mechanisms.
64 a cells on myelin is reversibly modulated
by NgR1 during differentiation and dedifferentiation proces
65 These studies revealed that
central NgR1 surfaces form a bridge between two copies of viral
66 In the healthy
CNS,
NgR1 regulates dendritic spine shape and attenuates acti
67 In chronic rat spinal
contusion,
NgR1 decoy treatment from 4 to 6 months after injury res
68 A soluble
decoy (
NgR1-Fc, AXER-204) blocks these ligands and provides a m
69 te that four different schizophrenia-
derived NgR1 variants fail to transduce myelin signals into axon
70 ibits the degradation of ID1 to
downregulate NgR1 expression.
71 In primary cortical neurons,
ectopic NgR1 inhibits FGF2-elicited axonal branching.
72 Our results show that loss of
either NgR1 or NgR3 causes axons to stall in the midline area a
73 as dominant negatives to disrupt
endogenous NgR1.
74 The data suggest that B cells
express NgR1 and NgR3 during EAE, being localized to infiltrates
75 Meningeal B-cells
expressing NgR1 and NgR3 were identified within the lumbosacral spi
76 rface receptors of the Nogo Receptor
family (
NgR1, NgR2, and NgR3) restrict excitatory synapse format
77 We demonstrate the Nogo receptor
family (
NgR1-3) acts as Abeta receptors mediating an inhibition
78 Finally,
NgR1(-/-) RGCs are strongly inhibited by MAG.
79 trong affinity for PrP(C), weak affinity
for NgR1, and no detectable affinity for LilrB2.
80 1 synapses uncovered a synaptic function
for NgR1.
81 ted in primary cortical neurons derived
from NgR1 null mice.
82 y were decreased in cultured OB neurons
from NgR1-KO mice.
83 etic interaction because double-
heterozygous NgR1(+/-), PlexinA2(+/-) neurons, but not single-heteroz
84 To elucidate
how NgR1 mediates cell binding and entry of reovirus, we def
85 In the presence of VCN,
however,
NgR1(-/-) RGCs exhibit enhanced neurite growth.
86 Human NgR1 functions as a reovirus receptor in vitro and is ex
87 Human NgR1 serves as a receptor for mammalian orthoreovirus (r
88 evidence that certain disease-derived
human NgR1 variants are dysfunctional proteins in vitro.
89 In non-neuronal cells, coexpression of
human NgR1, p75 and LINGO-1 conferred responsiveness to oligod
90 Collectively, our results
identify NgR1 and NgR3 as CSPG receptors, suggest that there is f
91 collapse that is significantly attenuated
in NgR1-null neurons compared with wild-type controls.
92 density caudal to the injury is detected
in NgR1 decoy-treated animals by immunohistology and by pos
93 Here, we examined proteins enriched
in NgR1 immunoprecipitates by Nogo-A exposure, identifying
94 ffusible inhibitor of regenerative growth
in NgR1-expressing axons.
95 In juvenile mice, LTD
in NgR1(-/-), but not PirB(-/-), slices is absent.
96 2-elicited enhancement of hippocampal LTP
in NgR1 mutants.
97 GFP revealed significant CST regeneration
in NgR1 knock-out mice.
98 Greater post-injury sprouting
in NgR1(+/-), PlexinA2(+/-) mice supports enhanced neurolog
99 increased in LOTUS-KO mice, whereas those
in NgR1-KO mice were decreased.
100 th aged and young adult mice, stroke
induces NgR1 ligands and down-regulates NgR1 inhibitors during t
101 ince this linkage was not detected in
intact NgR1 or a slightly larger fragment containing Cys-335 an
102 rate pharmacological experiment,
intrathecal NgR1 decoy protein administration was initiated 3 months
103 lin were shown to be generated from
isolated NgR1- and NgR3-expressing B-cells of ngr1(+/+) EAE-induc
104 Mice
lacking NgR1 protein exhibit reduced working memory function, co
105 We used mice
lacking NgR1 to test whether NgR1 functions as a reovirus neural
106 lyzed the disulfide structure of full-
length NgR1.
107 The receptor of the Nogo
ligand (
NgR1) was selected as the top candidate through Differen
108 on beyond the injury site in either Nogo/
MAG/
NgR1 triple mutants or NgR1 single mutants.
109 gnaling can improve neuron outgrowth,
making NgR1 an important therapeutic target for diverse neurolo
110 The Nogo receptor family
members NgR1 and NgR2 bind to MAIs and have been implicated in n
111 mposed of the structurally related
molecules NgR1, NgR2, and NgR3.
112 ordantly, expression of human but not
murine NgR1 confers reovirus binding and infection of nonsuscep
113 routes of inoculation, we found that
murine NgR1 is dispensable for reovirus dissemination to the CN
114 ults, shRNAi-mediated knock-down of
neuronal NgR1 does not result in a substantial release of L-MAG (
115 To examine the contribution of
neuronal NgR1 to outgrowth inhibition, we used two different stra
116 udies with Nogo-66, we propose that
neuronal NgR1 has a circumscribed role in regulating cytoskeletal
117 ndent synaptic strength and uncover
neuronal NgR1 as a regulator of synaptic plasticity.
118 trauma, interaction of Nogo-A with
neuronal NgR1 limits regenerative axonal sprouting and functional
119 In
neurons NgR1 and NgR2 support MAG binding in a sialic acid-depen
120 hat bind to a neuronal Nogo-66 receptor (
NgR/
NgR1) to limit axonal regeneration after central nervous
121 Thus, neither JAM-A
nor NgR1 is required for reovirus CNS tropism in mice, sugge
122 cap domain and stalk region of NgR2, but
not NgR1, are sufficient for MAG binding, and when expressed
123 These data introduce Olfm1 as a
novel NgR1 ligand that may modulate the functions of the NgR1
124 etion of disulfide loop Cys(309)-Cys(336)
of NgR1 selectively increases its affinity for Nogo-66 and
125 Genetic ablation
of NgR1 did not alter reovirus replication in the intestine
126 wo different strategies, genetic ablation
of NgR1 through the germline and transient short hairpin RN
127 The absence
of NgR1 also did not alter reovirus replication, neural tro
128 ntrathecal and intravenous administration
of NgR1-Fc to cynomolgus monkey and to rat are without evid
129 Here, biochemical analysis
of NgR1 function uncovered a physical complex with CRMP cyt
130 The Nogo-A-induced association
of NgR1 with CRMP2 requires PlexinA2 as a coreceptor.
131 The LRR cluster
of NgR1 supports binding of Nogo-66, OMgp, and MAG.
132 th vehicle (n = 6) or 0.10-0.17 mg/kg/day
of NgR1-Fc (n = 8) delivered via intrathecal lumbar cathete
133 Conditional deletion
of NgR1 in the chronic state results in gradual improvement
134 neration is abolished by genetic deletion
of NgR1.
135 ve when assessing options for development
of NgR1-based therapeutics for central nervous system injur
136 rimary human glioblastoma, downregulation
of NgR1 expression is associated with highly infiltrative c
137 Introduction of the shed ectodomain
of NgR1 is sufficient to accelerate excitatory synapse form
138 Expression
of NgR1 confers reovirus binding and infection of nonsuscep
139 rategies aimed at reactivating expression
of NgR1 will improve the clinical outcome of glioblastoma p
140 stal structures of a recombinant fragment
of NgR1 had revealed a disulfide linkage between Cys-266 an
141 that the human but not the murine homolog
of NgR1 functions as a receptor and confers efficient reovi
142 Olfm1 caused the inhibition
of NgR1 signaling by interfering with interaction between N
143 In addition, loss
of NgR1 attenuates long-term depression of synaptic transmi
144 Together, our findings reveal that loss
of NgR1 drives myelin-associated infiltration of glioblasto
145 The loss
of NgR1 function in adulthood eliminates spontaneous fear r
146 Loss
of NgR1 leads to FGF2-dependent enhancement of long-term po
147 Loss
of NgR1 leads to increased phosphorylation of extracellular
148 Loss
of NgR1 results in altered spine morphologies along apical
149 OMgp strongly inhibits neurite outgrowth
of NgR1 wild-type and mutant sensory neurons.
150 inase) pathway, without the participation
of NgR1.
151 ies have shown that the entire LRR region
of NgR1, including the C-terminal cap of the LRR, LRRCT, is
152 To assess a potential role
of NgR1 and NgR3 in axon guidance, we downregulated them us
153 se data provide a perspective on the role
of NgR1 ligand function in OPC fate in the context of a spe
154 ort a role for MT3-MMP-dependent shedding
of NgR1 in regulating excitatory synapse development.SIGNIF
155 In vitro BAFF stimulation
of NgR1- and NgR3-expressing B cells, directed them into th
156 Neural expression studies
of NgR1 and NgR2 have revealed broad and overlapping, yet d
157 Although the LRR domains
on NgR1 are necessary for binding to the myelin proteins, t
158 Gain and loss of function studies
on NgR1 elucidated its underlying molecular importance in s
159 te in either Nogo/MAG/NgR1 triple mutants
or NgR1 single mutants.
160 binds to NgR1 and can replace p75 in the
p75/
NgR1/LINGO-1 complex to activate RhoA in the presence of
161 ve focused on the role of NgRs,
particularly NgR1, in axonal regeneration in the injured adult CNS.
162 r, our findings establish that
physiological NgR1 signaling regulates activity-dependent synaptic str
163 PlexinA4 double mutants or PlexinA3/
PlexinA4/
NgR1 triple mutants through a complete transection injur
164 ly of proteins named Nogo receptor
proteins (
NgR1 to NgR3) regulates Abeta production via interaction
165 ng by co-incubation with recombinant BAFF-
R,
NgR1-Fc, or NgR3 peptides, the B cells remained in the G
166 NAQLR located in the third LRR domain of
rat NgR1.
167 ligand-binding subunit (the Nogo-66
receptor NgR1) and a signal transducing subunit (the neurotrophin
168 ors, Nogo and MAG, and their common
receptor NgR1 (or NgR).
169 Nogo-A and its
receptor NgR1 are present at cortical synapses.
170 emonstrate that reovirus binds Nogo
receptor NgR1, a leucine-rich repeat protein expressed in the CNS
171 The expression of Nogo-A and the
receptor NgR1 limits the recovery of adult mammals from central n
172 r complex comprised of the Nogo-66
receptor (
NgR1) and two transmembrane co-receptors p75/TROY and LI
173 ns and in vivo We identify Nogo-66
receptor (
NgR1) as an MT3-MMP substrate that is required for MT3-M
174 Nogo-66
receptor (
NgR1) is a leucine-rich repeat (LRR) protein that forms
175 The Nogo-66
receptor (
NgR1) is a promiscuous receptor for the myelin inhibitor
176 Nogo-A (Reticulon 4A) and Nogo-66
receptor (
NgR1) limit adult CNS axonal growth after injury is supp
177 We also detected a Nogo-66
receptor (
NgR1)-interacting Nogo-66 domain on the exosome surface.
178 hrough interaction with the Nogo A
receptor (
NgR1) complex.
179 rived inhibitors with soluble Nogo
receptor (
NgR1, RTN4R) decoy protein.
180 estigate the effect of Nogo-A/Nogo-
Receptor (
NgR1) pathway blockers.
181 The Nogo66
receptor (
NgR1) is a neuronal, leucine-rich repeat (LRR) protein t
182 We identify Nogo-66
receptors (
NgR1) as a downstream target of MT3-MMP proteolytic acti
183 Nogo-66
receptors (
NgR1-3) are glycosylphosphatidyl inositol-linked protein
184 Nogo
receptors (
NgR1, NgR2, and NgR3) are growth cone directive molecule
185 roke induces NgR1 ligands and down-
regulates NgR1 inhibitors during the peak OPC maturation block.
186 Incubating reovirus virions with
soluble NgR1 neutralizes infectivity.
187 gR1, we examined a series of Ala-
substituted NgR1 mutants for ligand binding activity.
188 Furthermore, processing of
surface NgR1 by MT3-MMP generates a soluble ectodomain fragment
189 ever, in reconstituted non-neuronal
systems,
NgR1 and p75 together are unable to activate RhoA, sugge
190 NgR2 directly and with greater affinity
than NgR1.
191 In the current study we define
that NgR1 and its homologs may contribute to immune cell sign
192 Regional gene disruption demonstrates
that NgR1 expression is required in both the basolateral amyg
193 We found
that NgR1 and NgR3 bind with high affinity to the glycosamino
194 ysis of synaptosomal fractions revealed
that NgR1 is enriched synaptically in the hippocampus.
195 Here, we show
that NgR1 and NgR3 mRNAs are expressed during spinal cord dev
196 We show
that NgR1 inhibits the formation of new synapses in the posts
197 In addition, we also show
that NgR1, but not NgR3, requires neuronal PlexinA2 for the r
198 The data show
that NgR1-Fc does not have preclinical toxicological issues i
199 These findings suggest
that NgR1, a receptor previously shown to restrict axon growt
200 le in WT and NgR1(-/-) mice, suggesting
that NgR1 is dispensable for reovirus neural spread to the CN
201 This suggests
that NgR1 and PirB participate in ligand-dependent inhibition
202 The NgR1-Fc group tissue exhibited a significant 2-3-fold in
203 bitors, indicating that Olfm1 attenuates
the NgR1 receptor functions.
204 We eliminated
the NgR1 pathway genetically in mice by conditional gene tar
205 ion that other receptors are involved in
the NgR1 complex.
206 e that AMIGO3 substitutes for LINGO-1 in
the NgR1-p75/TROY inhibitory signalling complex and suggests
207 igand that may modulate the functions of
the NgR1 complex in axonal growth.
208 adjacent C-terminal region (CT stalk) of
the NgR1 contributes to interaction with its coreceptors.
209 We find that regardless of
the NgR1 genotype, membrane-bound MAG strongly inhibits neur
210 in the middle of the concave surface of
the NgR1 leucine-rich repeat domain and surrounded by differ
211 de structure in the C-terminal region of
the NgR1, wherein the two Cys residues, Cys-335 and Cys-336,
212 is an additional functional component of
the NgR1/p75 signaling complex.
213 ory signalling complex and suggests that
the NgR1-p75/TROY-AMIGO3 receptor complex mediates myelin-in
214 endrocyte differentiation occurs through
the NgR1/Lingo-1 receptor complex.
215 purified 22-kDa protein containing all
three NgR1- and PirB-interacting domains (Nogo-22) is a substa
216 Although all
three NgR1-interacting domains of Nogo-A also interact with Pi
217 ndrocyte Nogo-A inhibition of growth
through NgR1 is thought to have little molecular relationship to
218 d share neuronal receptor mechanisms
through NgR1 and PirB.
219 Thus,
NgR1 determines the low set point for synaptic turnover
220 Thus,
NgR1 is the predominant receptor for Nogo-22 in regenera
221 Thus,
NgR1 robustly inhibits elimination of fear expression in
222 FGF2 bind directly and with high affinity
to NgR1 but not to NgR2 or NgR3.
223 ltiple structurally distinct ligands bind
to NgR1, we examined a series of Ala-substituted NgR1 mutan
224 Disruption of ligand binding
to NgR1 and subsequent signaling can improve neuron outgrow
225 igodendrocyte myelin glycoprotein binding
to NgR1 with IC50 values of 120, 14, and 4.5 nm, respective
226 sed in postnatal and adult neurons, binds
to NgR1 and can replace p75 in the p75/NgR1/LINGO-1 complex
227 Olfm1 specifically binds
to NgR1, as judged by alkaline phosphatase assay and coimmu
228 After injury to the corticospinal
tract,
NgR1 limits axon collateral sprouting but is not importa
229 We show here that the other
two NgR1-interacting domains, Nogo-A-24 and Nogo-C39, also b
230 gp, Nogo-66, and MAG compared with wild-
type NgR1 or NgR2.
231 a well-known antipsychotic drug,
upregulates NgR1 by post-translational targeting of USP1, which sens
232 ificant poststroke motor recovery, even
when NgR1 blockade is provided during the chronic time points
233 To determine
whether NgR1 functions in reovirus neuropathogenesis, we compare
234 We used mice lacking NgR1 to test
whether NgR1 functions as a reovirus neural receptor.
235 targeting all three myelin ligands, as
with NgR1 decoy receptor, provides the optimal chance for ove
236 neurite outgrowth but fail to associate
with NgR1 or NgR2.
237 Olfm1 is coexpressed
with NgR1 in dorsal root ganglia and retinal ganglion cells i
238 ith MAG with a higher affinity compared
with NgR1.
239 ation of a role for PlexinA2 in concert
with NgR1 after adult trauma.
240 AMIGO3 interacted functionally
with NgR1-p75/TROY in non-neuronal cells and in brain lysates
241 two separate domains are known interact
with NgR1.
242 ggesting a trivalent Nogo-A interaction
with NgR1.
243 nanomolar interactions of RTN2 and RTN3
with NgR1.
244 ing myelin-derived inhibitors signaling
with NgR1 decoy augments recovery from chronic spinal cord in