TY - JOUR
T1 - Nogo receptor antagonist LOTUS exerts suppression on axonal growth-inhibiting receptor PIR-B
AU - Kurihara, Yuji
AU - Takai, Toshiyuki
AU - Takei, Kohtaro
N1 - Funding Information:
This work was supported by grants from a Grant-in-Aid for Scientific Research (KAKENHI) from Japan Society for the Promotion of Science (JSPS) (JSPS KAKENHI Grant Numbers JP26870480 to Y.K., JP26290024 to K.T., and JP17H03561 to K.T.) and from The Ministry of Education, Culture, Sports, Science and Technology (MEXT) (MEXT KAKENHI Grant Number JP24111539 to K.T.), from Yokohama Academic Foundation (to Y.K.), from Narishige Neuroscience Research Foundation (to Y.K.), and from The Naito Foundation (to K.T.). We are grateful to Dr. Stephen M. Strittmatter at Yale University for kindly providing Ngr1-deficient mice, and Ms. Eriko Saito and Ms. Miyuki Ogawara at Yokohama City University for their technical assistances. All experiments were conducted in compliance with the ARRIVE guidelines.
Funding Information:
This work was supported by grants from a Grant‐in‐Aid for Scientific Research (KAKENHI) from Japan Society for the Promotion of Science (JSPS) (JSPS KAKENHI Grant Numbers JP26870480 to Y.K., JP26290024 to K.T., and JP17H03561 to K.T.) and from The Ministry of Education, Culture, Sports, Science and Technology (MEXT) (MEXT KAKENHI Grant Number JP24111539 to K.T.), from Yokohama Academic Foundation (to Y.K.), from Narishige Neuroscience Research Foundation (to Y.K.), and from The Naito Foundation (to K.T.). We are grateful to Dr. Stephen M. Strittmatter at Yale University for kindly providing ‐deficient mice, and Ms. Eriko Saito and Ms. Miyuki Ogawara at Yokohama City University for their technical assistances. All experiments were conducted in compliance with the ARRIVE guidelines. Ngr1
Publisher Copyright:
© 2020 International Society for Neurochemistry
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Damaged axons in the adult mammalian central nervous system have a restricted regenerative capacity mainly because of Nogo protein, which is a major myelin-associated axonal growth inhibitor with binding to both receptors of Nogo receptor-1 (NgR1) and paired immunoglobulin-like receptor (PIR)-B. Lateral olfactory tract usher substance (LOTUS) exerts complete suppression of NgR1-mediated axonal growth inhibition by antagonizing NgR1. However, the regulation of PIR-B functions in neurons remains unknown. In this study, protein–protein interactions analyses found that LOTUS binds to PIR-B and abolishes Nogo-binding to PIR-B completely. Reverse transcription-polymerase chain reaction and immunocytochemistry revealed that PIR-B is expressed in dorsal root ganglions (DRGs) from wild-type and Ngr1-deficient mice (male and female). In these DRG neurons, Nogo induced growth cone collapse and neurite outgrowth inhibition, but treatment with the soluble form of LOTUS completely suppressed them. Moreover, Nogo-induced growth cone collapse and neurite outgrowth inhibition in Ngr1-deficient DRG neurons were neutralized by PIR-B function-blocking antibodies, indicating that these Nogo-induced phenomena were mediated by PIR-B. Our data show that LOTUS negatively regulates a PIR-B function. LOTUS thus exerts an antagonistic action on both receptors of NgR1 and PIR-B. This may lead to an improvement in the defective regeneration of axons following injury. (Figure presented.).
AB - Damaged axons in the adult mammalian central nervous system have a restricted regenerative capacity mainly because of Nogo protein, which is a major myelin-associated axonal growth inhibitor with binding to both receptors of Nogo receptor-1 (NgR1) and paired immunoglobulin-like receptor (PIR)-B. Lateral olfactory tract usher substance (LOTUS) exerts complete suppression of NgR1-mediated axonal growth inhibition by antagonizing NgR1. However, the regulation of PIR-B functions in neurons remains unknown. In this study, protein–protein interactions analyses found that LOTUS binds to PIR-B and abolishes Nogo-binding to PIR-B completely. Reverse transcription-polymerase chain reaction and immunocytochemistry revealed that PIR-B is expressed in dorsal root ganglions (DRGs) from wild-type and Ngr1-deficient mice (male and female). In these DRG neurons, Nogo induced growth cone collapse and neurite outgrowth inhibition, but treatment with the soluble form of LOTUS completely suppressed them. Moreover, Nogo-induced growth cone collapse and neurite outgrowth inhibition in Ngr1-deficient DRG neurons were neutralized by PIR-B function-blocking antibodies, indicating that these Nogo-induced phenomena were mediated by PIR-B. Our data show that LOTUS negatively regulates a PIR-B function. LOTUS thus exerts an antagonistic action on both receptors of NgR1 and PIR-B. This may lead to an improvement in the defective regeneration of axons following injury. (Figure presented.).
KW - Nogo-A
KW - axonal growth inhibition
KW - lateral olfactory tract usher substance
KW - paired immunoglobulin-like receptor-B
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U2 - 10.1111/jnc.15013
DO - 10.1111/jnc.15013
M3 - Article
C2 - 32201946
AN - SCOPUS:85083322277
VL - 155
SP - 285
EP - 299
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 3
ER -