The Role of Zyxin in Regulating Platelet Cytoskeleton Distribution / 中国实验血液学杂志

OBJECTIVE@#To investigate the regulatory effect of zyxin on the distribution of platelet cytoskeleton.@*METHODS@#Platelets were isolated from zyxin-knockout (Zyx@*RESULTS@#After zyxin gene was knockout, the expressions of cytoskeleton proteins β-actin, α-actinin, filamin A, and myosin Ⅱ A in resting and Jas-induced platelets were significantly increased. In the platelet spreading on fibrinogen surface, F-actin was increased in Zyx@*CONCLUSION@#Zyxin significantly regulates the distribution of platelet cytoskeleton, which plays an important role in maintaining platelet cytoskeleton homeostasis.

Estudo da expressão e participação de VASP e Zyxin na diferenciação hematopoiética, na leucemia mieloide crônica e na via de sinalização BCR-ABL / VASP and Zyxin expression and participation in hematopoietic differentiation, in chronic myeloid leukemia and BCR-ABL signaling pathway

VASP (Vasodilator-stimulated phosphoprotein) e Zyxin são proteínas reguladoras de actina que controlam a adesão célula-célula. Zyxin dirige a montagem da actina através da interação e recrutamento da VASP a sítios específicos da adesão. A fosforilação da VASP ou da Zyxin altera suas atividades nas junções aderentes. PKA fosforila VASP em serina 157, regulando, assim, importantes funções celulares de VASP. VASP interage com ABL e é substrato da oncoproteína BCR-ABL. A presença da proteína BCR-ABL promove a oncogênese em pacientes com leucemia mieloide crônica (LMC) devido à ativação constitutiva da atividade tirosina quinase. Apesar de já descrita alteração da expressão de VASP e Zyxin em diferentes tumores epiteliais, o papel de VASP e Zyxin na LMC, na via de sinalização BCR-ABL e a participação destas proteínas na hematopoiese são desconhecidos. Desta maneira, demonstramos aqui ausência de p-VASP ser157 em células de medula óssea de pacientes com LMC, em contraste com a presença de p-VASP ser157 em doadores saudáveis. Pacientes com LMC em remissão, responsivos a inibidores de tirosina quinase, apresentam p-VASP ser157, enquanto os pacientes resistentes não expressam p-VASP ser157. Utilizando células K562 inibidas para VASP ou Zyxin, observamos que VASP e Zyxin modulam as proteínas anti-apoptóticas BCL-2 e BCL-XL da via de sinalização do BCR-ABL. Em adição, células K562 silenciadas para a VASP apresentam diminuição na atividade de FAK y925 e demonstramos que VASP interage com FAK. A expressão de VASP e Zyxin e de suas formas ativas aumenta durante a diferenciação megacariocítica e a inibição de VASP implica em diminuição na expressão do marcador CD61. Identificamos no presente estudo a participação de VASP e Zyxin na via do BCR-ABL, regulando a expressão de proteínas efetoras anti-apoptóticas e, também, na diferenciação megacariocítica...

VASP (vasodilator-stimulated phosphoprotein) and Zyxin are actin regulatory proteins that control cell-cell adhesion. Zyxin directs actin assembly by interacting and recruiting VASP to specific sites of adhesion. The phosphorylation of VASP and Zyxin modifies their activity in cell-cell junctions. PKA phosphorylates VASP at serine 157 regulating VASP cellular functions. VASP interacts with ABL and VASP is a substrate of BCR-ABL oncoprotein. The presence of BCR-ABL protein drives oncogenesis in patients with chronic myeloid leukemia (CML) due to a constitutive activation of tyrosine kinase activity. It has been described an altered expression of VASP and Zyxin in different types of tumor; however the function of VASP and Zyxin in CML, in BCR-ABL pathway and in hematopoiesis remains unknown. We describe here the absence of p-VASP ser157 in CML bone marrow cells, in contrast to p-VASP ser157 expression in healthy donors. Patients responsive to tyrosine kinase inhibitors present p-VASP ser157, while resistant patients do not have p-VASP ser157. In K562 cells we observed that VASP and Zyxin modulate anti-apoptotic proteins BCL-2 and BCL-XL. VASP depletion in K562 cells decreases FAK y925 activity and VASP interacts with FAK. Expression of VASP, p-VASP, Zyxin and p-Zyxin increases during megakaryocyte differentiation and VASP inhibition affects this differentiation through reduced CD61 expression in VASP depleted cells. We identify here the participation of VASP and Zyxin in BCR-ABL pathway affecting anti-apoptotic proteins and, also, in megakaryocyte differentiation. Then, the altered expression of VASP activity in CML patients may contribute to CML pathogenesis, affecting cellular differentiation or leukemic cell adhesion...

Advances in research on the target antigens of antisperm antibodies / 中华男科学杂志

Antisperm antibodies can lead to immunological infertility. Further research on the target antigens of antisperm antibodies may help to discover the causal relationship of antisperm antibodies to infertility. This paper summarizes the structure and function of the six target antigens of antisperm antibodies found recently, so as to discover the causal relationship of the antibodies to infertility and provide a basis for screening a vaccine for immunological contraception.