NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans

被引：366

作者：

Dickendesher, Travis L. ^{[1
,2
]}

Baldwin, Katherine T. ^{[2
,3
]}

Mironova, Yevgeniya A. ^{[2
,3
]}

Koriyama, Yoshiki ^{[4
,5
,6
]}

Raiker, Stephen J. ^{[2
,7
]}

Askew, Kim L. ^{[8
]}

Wood, Andrew ^{[8
]}

Geoffroy, Cedric G. ^{[9
]}

Zheng, Binhai ^{[9
]}

Liepmann, Claire D. ^{[10
]}

Katagiri, Yasuhiro ^{[10
]}

Benowitz, Larry I. ^{[4
,5
,6
,11
]}

Geller, Herbert M. ^{[10
]}

Giger, Roman J. ^{[1
,2
,3
,12
]}

机构：

[1] Univ Michigan, Sch Med, Neurosci Program, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI USA

[3] Univ Michigan, Sch Med, Cellular & Mol Biol Program, Ann Arbor, MI USA

[4] Harvard Univ, Childrens Hosp, Sch Med, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA

[5] Harvard Univ, Childrens Hosp, Sch Med, Lab Neurosci Res Neurosurg, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA

[7] Univ Rochester, Sch Med & Dent, Dept Biomed Genet, Rochester, NY USA

[8] Pfizer Global Res & Dev, Neurosci Res Unit, Groton, CT USA

[9] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA

[10] NHLBI, Dev Neurobiol Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA

[11] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA

[12] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI USA

来源：

NATURE NEUROSCIENCE | 2012年 / 15卷 / 05期

关键词：

RETINAL GANGLION-CELLS; OLIGODENDROCYTE-MYELIN GLYCOPROTEIN; CORTICOSPINAL TRACT REGENERATION; SPINAL-CORD-INJURY; AXON REGENERATION; NOGO-66; RECEPTOR; NEURITE GROWTH; OPTIC-NERVE; FUNCTIONAL RECEPTOR; RECOVERY;

D O I：

10.1038/nn.3070

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

In the adult mammalian CNS, chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors (MAIs) stabilize neuronal structure and restrict compensatory sprouting following injury. The Nogo receptor family members NgR1 and NgR2 bind to MAIs and have been implicated in neuronal inhibition. We found that NgR1 and NgR3 bind with high affinity to the glycosaminoglycan moiety of proteoglycans and participate in CSPG inhibition in cultured neurons. Nogo receptor triple mutants (Ngr1(-/-); Ngr2(-/-); Ngr3(-/-); which are also known as Rtn4r, Rtn4rI2 and Rtn4rI1, respectively), but not single mutants, showed enhanced axonal regeneration following retro-orbital optic nerve crush injury. The combined loss of Ngr1 and Ngr3 (Ngr1(-/-); Ngr3(-/-)), but not Ngr1 and Ngr2 (Ngr1(-/-); Ngr2(-/-)), was sufficient to mimic the triple mutant regeneration phenotype. Regeneration in Ngr1(-/-); Ngr3(-/-) mice was further enhanced by simultaneous ablation of Rptp sigma (also known as Ptprs), a known CSPG receptor. Collectively, our results identify NgR1 and NgR3 as CSPG receptors, suggest that there is functional redundancy among CSPG receptors, and provide evidence for shared mechanisms of MAI and CSPG inhibition.

引用

页码：703 / 712

页数：10

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