Human LilrB2 Is a β-Amyloid Receptor and Its Murine Homolog PirB Regulates Synaptic Plasticity in an Alzheimer's Model

被引：386

作者：

Kim, Taeho ^{[1
,2
]}

Vidal, George S. ^{[1
,2
]}

Djurisic, Maja ^{[1
,2
]}

William, Christopher M. ^{[3
]}

Birnbaum, Michael E. ^{[4
,5
]}

Garcia, K. Christopher ^{[4
,5
]}

Hyman, Bradley T. ^{[3
]}

Shatz, Carla J. ^{[1
,2
]}

机构：

[1] Stanford Univ, James H Clark Ctr, Dept Biol & Neurobiol, Stanford, CA 94305 USA

[2] Stanford Univ, James H Clark Ctr, Dept BioX, Stanford, CA 94305 USA

[3] Massachusetts Gen Hosp, Neuropathol Serv, Charlestown, MA 02129 USA

[4] Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA

[5] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA

来源：

SCIENCE | 2013年 / 341卷 / 6152期

关键词：

OCULAR-DOMINANCE PLASTICITY; PRION PROTEIN; MOUSE MODEL; MYELIN; DEPRESSION; COFILIN; DISEASE; DEPRIVATION; INHIBITION; IMPAIRMENT;

D O I：

10.1126/science.1242077

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Soluble beta-amyloid (A beta) oligomers impair synaptic plasticity and cause synaptic loss associated with Alzheimer's disease (AD). We report that murine PirB (paired immunoglobulin-like receptor B) and its human ortholog LilrB2 (leukocyte immunoglobulin-like receptor B2), present in human brain, are receptors for A beta oligomers, with nanomolar affinity. The first two extracellular immunoglobulin (Ig) domains of PirB and LilrB2 mediate this interaction, leading to enhanced cofilin signaling, also seen in human AD brains. In mice, the deleterious effect of A beta oligomers on hippocampal long-term potentiation required PirB, and in a transgenic model of AD, PirB not only contributed to memory deficits present in adult mice, but also mediated loss of synaptic plasticity in juvenile visual cortex. These findings imply that LilrB2 contributes to human AD neuropathology and suggest therapeutic uses of blocking LilrB2 function.

引用

收藏

页码：1399 / 1404

页数：6

相关论文

共 40 条

[1]

Neuroprotection from Stroke in the Absence of MHCI or PirB [J].

Adelson, Jaimie D. ;

Barreto, George E. ;

Xu, Lijun ;

Kim, Taeho ;

Brott, Barbara K. ;

Ouyang, Yi-Bing ;

Naserke, Thorsten ;

Djurisic, Maja ;

Xiong, Xiaoxing ;

Shatz, Carla J. ;

Giffard, Rona G. .

NEURON, 2012, 73 (06) :1100-1107

[2]

PirB is a Functional Receptor for Myelin Inhibitors of Axonal Regeneration [J].

Atwal, Jasvinder K. ;

Pinkston-Gosse, Julie ;

Syken, Josh ;

Stawicki, Scott ;

Wu, Yan ;

Shatz, Carla ;

Tessier-Lavigne, Marc .

SCIENCE, 2008, 322 (5903) :967-970

[3]

Reversing EphB2 depletion rescues cognitive functions in Alzheimer model [J].

Cisse, Moustapha ;

Halabisky, Brian ;

Harris, Julie ;

Devidze, Nino ;

Dubal, Dena B. ;

Sun, Binggui ;

Orr, Anna ;

Lotz, Gregor ;

Kim, Daniel H. ;

Hamto, Patricia ;

Ho, Kaitlyn ;

Yu, Gui-Qiu ;

Mucke, Lennart .

NATURE, 2011, 469 (7328) :47-52

[4]

Deprivation-induced synaptic depression by distinct mechanisms in different layers of mouse visual cortex [J].

Crozier, Robert A. ;

Wang, Yun ;

Liu, Cheng-Hang ;

Bear, Mark F. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (04) :1383-1388

[5]

Thy1-hAPPLond/Swe+ mouse model of Alzheimer's disease displays broad behavioral deficits in sensorimotor, cognitive and social function [J].

Faizi, Mehrdad ;

Bader, Patrick L. ;

Saw, Nay ;

Nguyen, Thuy-Vi V. ;

Beraki, Simret ;

Wyss-Coray, Tony ;

Longo, Frank M. ;

Shamloo, Mehrdad .

BRAIN AND BEHAVIOR, 2012, 2 (02) :142-154

[6]

Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity [J].

Fujita, Yuki ;

Endo, Shota ;

Takai, Toshiyuki ;

Yamashita, Toshihide .

EMBO JOURNAL, 2011, 30 (07) :1389-1401

[7]

Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease [J].

Garcia-Alloza, Monica ;

Robbins, Elissa M. ;

Zhang-Nunes, Sandy X. ;

Purcell, Susan M. ;

Betensky, Rebecca A. ;

Raju, Susan ;

Prada, Claudia ;

Greenberg, Steven M. ;

Bacskai, Brian J. ;

Frosch, Matthew P. .

NEUROBIOLOGY OF DISEASE, 2006, 24 (03) :516-524

[8]

AMPAR removal underlies Aβ-induced synaptic depression and dendritic spine loss [J].

Hsieh, Helen ;

Boehm, Jannic ;

Sato, Chihiro ;

Iwatsubo, Takeshi ;

Tomita, Taisuke ;

Sisodia, Sangram ;

Malinow, Roberto .

NEURON, 2006, 52 (05) :831-843

[9]

Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo:: evidence for augmentation of a 42-specific γ secretase [J].

Jankowsky, JL ;

Fadale, DJ ;

Anderson, J ;

Xu, GM ;

Gonzales, V ;

Jenkins, NA ;

Copeland, NG ;

Lee, MK ;

Younkin, LH ;

Wagner, SL ;

Younkin, SG ;

Borchelt, DR .

HUMAN MOLECULAR GENETICS, 2004, 13 (02) :159-170

[10]

FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer's disease [J].

Kam, Tae-In ;

Song, Sungmin ;

Gwon, Youngdae ;

Park, Hyejin ;

Yan, Ji-Jing ;

Im, Isak ;

Choi, Ji-Woo ;

Choi, Tae-Yong ;

Kim, Jeongyeon ;

Song, Dong-Keun ;

Takai, Toshiyuki ;

Kim, Yong-Chul ;

Kim, Key-Sun ;

Choi, Se-Young ;

Choi, Sukwoo ;

Klein, William L. ;

Yuan, Junying ;

Jung, Yong-Keun .

JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (07) :2791-2802

← 1 2 3 4 →