Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 120(46): e2215285120, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37931110

RESUMO

The insulin-like growth factor 2 (IGF2) plays critical roles in cell proliferation, migration, differentiation, and survival. Despite its importance, the molecular mechanisms mediating the trafficking of IGF2 along the secretory pathway remain unclear. Here, we utilized a Retention Using Selective Hook system to analyze molecular mechanisms that regulate the secretion of IGF2. We found that a type I transmembrane protein, TMED10, is essential for the secretion of IGF2 and for differentiation of mouse myoblast C2C12 cells. Further analyses indicate that the residues 112-140 in IGF2 are important for the secretion of IGF2 and these residues directly interact with the GOLD domain of TMED10. We then reconstituted the release of IGF2 into COPII vesicles. This assay suggests that TMED10 mediates the packaging of IGF2 into COPII vesicles to be efficiently delivered to the Golgi. Moreover, TMED10 also mediates ER export of TGN-localized cargo receptor, sortilin, which subsequently mediates TGN export of IGF2. These analyses indicate that TMED10 is critical for IGF2 secretion by directly regulating ER export and indirectly regulating TGN export of IGF2, providing insights into trafficking of IGF2 for myoblast differentiation.


Assuntos
Fator de Crescimento Insulin-Like II , Mioblastos , Via Secretória , Proteínas de Transporte Vesicular , Animais , Camundongos , Diferenciação Celular , Vesículas Revestidas pelo Complexo de Proteína do Envoltório/metabolismo , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Transporte Proteico , Proteínas de Transporte Vesicular/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo
2.
Sci Adv ; 9(42): eadi1891, 2023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37851799

RESUMO

Skeletal muscle regeneration requires the highly coordinated cooperation of muscle satellite cells (MuSCs) with other cellular components. Upon injury, myeloid cells populate the wound site, concomitant with MuSC activation. However, detailed analysis of MuSC-myeloid cell interaction is hindered by the lack of suitable live animal imaging technology. Here, we developed a dual-laser multimodal nonlinear optical microscope platform to study the dynamics of MuSCs and their interaction with nonmyogenic cells during muscle regeneration. Using three-dimensional time-lapse imaging on live reporter mice and taking advantages of the autofluorescence of reduced nicotinamide adenine dinucleotide (NADH), we studied the spatiotemporal interaction between nonmyogenic cells and muscle stem/progenitor cells during MuSC activation and proliferation. We discovered that their cell-cell contact was transient in nature. Moreover, MuSCs could activate with notably reduced infiltration of neutrophils and macrophages, and their proliferation, although dependent on macrophages, did not require constant contact with them. These findings provide a fresh perspective on myeloid cells' role during muscle regeneration.


Assuntos
Músculo Esquelético , Células Satélites de Músculo Esquelético , Camundongos , Animais , Músculo Esquelético/fisiologia , Regeneração , Microscopia Intravital , Células Mieloides
3.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33753492

RESUMO

Adult mouse muscle satellite cells (MuSCs) are quiescent in uninjured muscles. Upon muscle injury, MuSCs exit quiescence, reenter the cell cycle to proliferate and self-renew, and then differentiate and fuse to drive muscle regeneration. However, it remains poorly understood how MuSCs transition from quiescence to the cycling state. Here, we report that Pax3 and Pax7 binding protein 1 (Paxbp1) controls a key checkpoint during this critical transition. Deletion of Paxbp1 in adult MuSCs prevented them from reentering the cell cycle upon injury, resulting in a total regeneration failure. Mechanistically, we found an abnormal elevation of reactive oxygen species (ROS) in Paxbp1-null MuSCs, which induced p53 activation and impaired mTORC1 signaling, leading to defective cell growth, apoptosis, and failure in S-phase reentry. Deliberate ROS reduction partially rescued the cell-cycle reentry defect in mutant MuSCs. Our study reveals that Paxbp1 regulates a late cell-growth checkpoint essential for quiescent MuSCs to reenter the cell cycle upon activation.


Assuntos
Células-Tronco Adultas/fisiologia , Pontos de Checagem do Ciclo Celular , Proteínas Nucleares/metabolismo , Células Satélites de Músculo Esquelético/fisiologia , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Técnicas de Inativação de Genes , Microscopia Intravital , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Nucleares/genética , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismo , Imagem com Lapso de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...