Diverse functions of kindlin/fermitin proteins during embryonic development in Xenopus laevis.
Diverse functions of kindlin/fermitin proteins during embryonic development in Xenopus laevis.
复制标题
Xenopus laevis中胚胎发育过程中Kindlin/Fermitin蛋白的各种功能。
DOI：
10.1016/j.mod.2014.07.004
复制
发表时间：
2014-08
影响因子：
2.6
通讯作者：
DeSimone, Douglas W.
中科院分区：
文献类型：
--
作者：
Rozario, Tania;Mead, Paul E.;DeSimone, Douglas W.
Kindlin/Fermitin家族包括三种参与调节整联蛋白配体结合活性和粘附的蛋白质。kindlin 1和3中的功能缺失突变分别与Kindler综合征和白细胞粘附缺陷III（LAD-III）有关，而kindlin 2缺失小鼠是胚胎致死的。长期以来，细胞-细胞和细胞-ECM粘附的翻译后调节一直被认为对形态发生很重要，然而，在正常发育中粘附分子功能的激活依赖性变化的具体例子很少报道。在这项研究中，反义morpholinos被用来减少表达的个别kindlin非洲爪蟾胚胎，以探讨其在早期发育中的作用。Kindlin 1基因敲除导致发育迟缓、肠道严重畸形，并最终在蝌蚪阶段致死。Kindlin 2变形胚胎在血管维持和血管生成分支方面表现出晚期缺陷，这与小鼠中Kindlin 2功能丧失一致。反义吗啉代也被用于消耗卵母细胞和卵子中的母体kindlin 2蛋白。缺乏母体kindlin 2的胚胎由于胞质分裂失败而在早期卵裂阶段停滞。Kindlin 3形态变体表型包括表皮纤毛跳动的缺陷和尾芽阶段的部分麻痹，但这些胚胎最终随着吗啉水平的下降而恢复。这些结果表明kindlin在脊椎动物发育中的功能范围非常广泛。
The kindlin/fermitin family includes three proteins involved in regulating integrin ligand-binding activity and adhesion. Loss-of-function mutations in kindlins1 and 3 have been implicated in Kindler Syndrome and Leukocyte Adhesion Deficiency III (LAD-III) respectively, whereas kindlin2 null mice are embryonic lethal. Post translational regulation of cell-cell and cell-ECM adhesion has long been presumed to be important for morphogenesis, however, few specific examples of activation-dependent changes in adhesion molecule function in normal development have been reported. In this study, antisense morpholinos were used to reduce expression of individual kindlins in Xenopus laevis embryos in order to investigate their roles in early development. Kindlin1 knockdown resulted in developmental delays, gross malformations of the gut and eventual lethality by tadpole stages. Kindlin2 morphant embryos displayed late stage defects in vascular maintenance and angiogenic branching consistent with kindlin2 loss of function in the mouse. Antisense morpholinos were also used to deplete maternal kindlin2 protein in oocytes and eggs. Embryos lacking maternal kindlin2 arrested at early cleavage stages due to failures in cytokinesis. Kindlin3 morphant phenotypes included defects in epidermal ciliary beating and partial paralysis at tailbud stages but these embryos recovered eventually as morpholino levels decayed. These results indicate a remarkably diverse range of kindlin functions in vertebrate development.
登录
查看更多内容
DOI：
10.1111/j.1549-8719.2010.00025.x
发表时间：
2010-04
期刊：
Microcirculation (New York, N.Y. : 1994)
影响因子：
--
作者：
Culver JC;Dickinson ME
通讯作者：
Dickinson ME
影响因子：
20.3
作者：
Franco, Marcela;Roswall, Pernilla;Pietras, Kristian
通讯作者：
Pietras, Kristian
DOI：
10.1074/jbc.m109.085746
发表时间：
2010-06-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bialkowska K;Ma YQ;Bledzka K;Sossey-Alaoui K;Izem L;Zhang X;Malinin N;Qin J;Byzova T;Plow EF
通讯作者：
Plow EF
影响因子：
4
作者：
Bandyopadhyay, Aditi;Rothschild, Gerson;Raghavan, Srikala
通讯作者：
Raghavan, Srikala
影响因子：
64.8
作者：
Hellstroem, Mats;Phng, Li-Kun;Betsholtz, Christer
通讯作者：
Betsholtz, Christer