The endocytic adaptor Numb regulates thymus size by modulating pre-TCR signaling during asymmetric division

被引：17

作者：

Aguado, Rocio ^{[1
]}

Martin-Blanco, Nadia ^{[1
]}

Caraballo, Michael ^{[1
]}

Canelles, Matilde ^{[1
]}

机构：

[1] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain

来源：

BLOOD | 2010年 / 116卷 / 10期

关键词：

T-CELL-RECEPTOR; MAMMALIAN NUMB; DEVELOPMENTAL PROGRESSION; HEMATOPOIETIC STEM; LINEAGE DECISION; PROGENITOR CELLS; DAUGHTER CELL; PROTEIN; NOTCH; PROLIFERATION;

D O I：

10.1182/blood-2009-10-246777

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Stem cells must proliferate and differentiate to generate the lineages that shape mature organs; understanding these 2 processes and their interaction is one of the central themes in current biomedicine. An intriguing aspect is asymmetric division, by which 2 daughter cells with different fates are generated. Several cell fate determinants participate in asymmetric division, with the endocytic adaptor Numb as the best-known example. Here, we have explored the role of asymmetric division in thymocyte development, visualizing the differential segregation of Numb and pre-TCR in thymic precursors. Analysis of mice where Numb had been inhibited by expressing a dominant negative revealed enhanced pre-T-cell receptor (TCR) signaling and a smaller thymus. Conversely, Numb overexpression resulted in loss of asymmetric division and a larger thymus. The conclusion is that Numb determines the levels of pre-TCR signaling in dividing thymocytes and, ultimately, the size of the pool from which mature T lymphocytes are selected. (Blood. 2010; 116(10):1705-1714)

引用

页码：1705 / 1714

页数：10

共 47 条

[1] Regulation of T-cell progenitor survival and cell-cycle entry by the pre-T-cell receptor [J].

Aifantis, I ;

Mandal, M ;

Sawai, K ;

Ferrando, A ;

Vilimas, T .

IMMUNOLOGICAL REVIEWS, 2006, 209 :159-169

[2] The Notch regulator Numb links the Notch and TCR signaling pathways [J].

Anderson, AC ;

Kitchens, EA ;

Chan, SW ;

Hill, CS ;

Jan, YN ;

Zhong, WM ;

Robey, EA .

JOURNAL OF IMMUNOLOGY, 2005, 174 (02) :890-897

[3] The endocytic protein α-adaptin is required for numb-mediated asymmetric cell division in Drosophila [J].

Berdnik, D ;

Török, T ;

González-Gaitán, M ;

Knoblich, JA .

DEVELOPMENTAL CELL, 2002, 3 (02) :221-231

[4] Integrin β cytoplasmic domain interactions with phosphotyrosine-binding domains:: A structural prototype for diversity in integrin signaling [J].

Calderwood, DA ;

Fujioka, Y ;

de Pereda, JM ;

García-Alvarez, B ;

Nakamoto, T ;

Margolis, B ;

McGlade, CJ ;

Liddington, RC ;

Ginsberg, MH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) :2272-2277

[5] The influence of the thymic environment on the CD4-versus-CD8 T lineage decision [J].

Canelles, M ;

Park, ML ;

Schwartz, OM ;

Fowlkes, BJ .

NATURE IMMUNOLOGY, 2003, 4 (08) :756-764

[6] Regulation of surface expression of the human pre-T cell receptor complex [J].

Carrasco, YR ;

Navarro, MN ;

de Yébenes, VG ;

Ramiro, AR ;

Toribio, ML .

SEMINARS IN IMMUNOLOGY, 2002, 14 (05) :325-334

[7] Asymmetric segregation of Numb:: a mechanism for neural specification from Drosophila to mammals [J].

Cayouette, M ;

Raff, M .

NATURE NEUROSCIENCE, 2002, 5 (12) :1265-1269

[8] Asymmetric T lymphocyte division in the initiation of adaptive immune responses [J].

Chang, John T. ;

Palanivel, Vikram R. ;

Kinjyo, Ichiko ;

Schambach, Felix ;

Intlekofer, Andrew M. ;

Banerjee, Arnob ;

Longworth, Sarah A. ;

Vinup, Kristine E. ;

Mrass, Paul ;

Oliaro, Jane ;

Killeen, Nigel ;

Orange, Jordan S. ;

Russell, Sarah M. ;

Weninger, Wolfgang ;

Reiner, Steven L. .

SCIENCE, 2007, 315 (5819) :1687-1691

[9] Obligatory role for cooperative signaling by pre-TCR and notch during thymocyte differentiation [J].

Ciofani, M ;

Schmitt, TM ;

Ciofani, A ;

Michie, AM ;

Çuburu, N ;

Aublin, A ;

Maryanski, JL ;

Zúñiga-Pflücker, JC .

JOURNAL OF IMMUNOLOGY, 2004, 172 (09) :5230-5239

[10] Characterization of four mammalian numb protein isoforms - Identification of cytoplasmic and membrane-associated variants of the phosphotyrosine binding domain [J].

Dho, SE ;

French, MB ;

Woods, SA ;

McGlade, CJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (46) :33097-33104

← 1 2 3 4 5 →