MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of haematopoietic stem cells.
MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of haematopoietic stem cells.
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DOI：
10.1038/s41467-021-22749-1
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发表时间：
2021-05-04
影响因子：
16.6
通讯作者：
Frenette PS
中科院分区：
文献类型：
--
作者：
Wei Q;Pinho S;Dong S;Pierce H;Li H;Nakahara F;Xu J;Xu C;Boulais PE;Zhang D;Maryanovich M;Cuervo AM;Frenette PS
Haematopoietic stem cells (HSCs) tightly regulate their quiescence, proliferation, and differentiation to generate blood cells during the entire lifetime. The mechanisms by which these critical activities are balanced are still unclear. Here, we report that Macrophage-Erythroblast Attacher (MAEA, also known as EMP), a receptor thus far only identified in erythroblastic island, is a membrane-associated E3 ubiquitin ligase subunit essential for HSC maintenance and lymphoid potential. Maea is highly expressed in HSCs and its deletion in mice severely impairs HSC quiescence and leads to a lethal myeloproliferative syndrome. Mechanistically, we have found that the surface expression of several haematopoietic cytokine receptors (e.g. MPL, FLT3) is stabilised in the absence of Maea, thereby prolonging their intracellular signalling. This is associated with impaired autophagy flux in HSCs but not in mature haematopoietic cells. Administration of receptor kinase inhibitor or autophagy-inducing compounds rescues the functional defects of Maea-deficient HSCs. Our results suggest that MAEA provides E3 ubiquitin ligase activity, guarding HSC function by restricting cytokine receptor signalling via autophagy. Haematopoietic stem cells (HSCs) are metabolically quiescent, with balanced myeloid and lymphoid potential. Here the authors show that MAEA is required in HSCs for ubiquitination and downregulation of surface cytokine receptors via autophagy; MAEA loss leads to impaired HSC quiescence and a myeloproliferative disorder.
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影响因子：
7.7
作者：
Lampert F;Stafa D;Goga A;Soste MV;Gilberto S;Olieric N;Picotti P;Stoffel M;Peter M
通讯作者：
Peter M
DOI：
10.1038/nrm3772
发表时间：
2014-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
32.4
作者：
Cordeiro Gomes A;Hara T;Lim VY;Herndler-Brandstetter D;Nevius E;Sugiyama T;Tani-Ichi S;Schlenner S;Richie E;Rodewald HR;Flavell RA;Nagasawa T;Ikuta K;Pereira JP
通讯作者：
Pereira JP
影响因子：
16.8
作者：
Moran-Crusio K;Reavie LB;Aifantis I
通讯作者：
Aifantis I
影响因子：
20.3
作者：
Lee, JCM;Gimm, JA;Chasis, JA
通讯作者：
Chasis, JA