PAR-3 and PAR-1 inhibit LET-99 localization to generate a cortical band important for spindle positioning in Caenorhabditis elegans embryos.
PAR-3 and PAR-1 inhibit LET-99 localization to generate a cortical band important for spindle positioning in Caenorhabditis elegans embryos.
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DOI：
10.1091/mbc.e07-02-0105
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发表时间：
2007-11
影响因子：
3.3
通讯作者：
Jui-Ching Wu;Lesilee S. Rose
中科院分区：
文献类型：
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作者：
Jui-Ching Wu;Lesilee S. Rose
保守的PAR蛋白定位于不对称皮质结构域，是许多生物体中细胞命运决定因素极化定位所必需的。在秀丽隐杆线虫胚胎中，LET-99和G蛋白信号传导作用于par的下游，调节纺锤体定位，确保不对称分裂。PAR-3和PAR-2通过一种未知的机制将LET-99定位于皮质后带。在这里，我们报告了LET-99的不对称性取决于皮质局部化的PAR-1和PAR-4，而不是细胞质极性效应。在par-1和par-4胚胎中，LET-99在整个后皮层积累，但在PAR-3占据的前皮层保持低水平。此外，PAR-3和PAR-1的皮层分布呈分级分布，分别在前极和后极水平最高，而这些蛋白的最低水平与LET-99的高积累相关。这些结果表明，PAR-3和PAR-1抑制了LET-99的定位，从而产生条带模式。此外，抑制LET-99的定位需要PAR-1激酶活性，并且PAR-1与LET-99相关。最后，对par-1胚胎的检查表明，LET-99的带状模式对于正常的后纺锤体位移和防止由细胞形状限制引起的纺锤体定向错误至关重要。
The conserved PAR proteins are localized in asymmetric cortical domains and are required for the polarized localization of cell fate determinants in many organisms. In Caenorhabditis elegans embryos, LET-99 and G protein signaling act downstream of the PARs to regulate spindle positioning and ensure asymmetric division. PAR-3 and PAR-2 localize LET-99 to a posterior cortical band through an unknown mechanism. Here we report that LET-99 asymmetry depends on cortically localized PAR-1 and PAR-4 but not on cytoplasmic polarity effectors. In par-1 and par-4 embryos, LET-99 accumulates at the entire posterior cortex, but remains at low levels at the anterior cortex occupied by PAR-3. Further, PAR-3 and PAR-1 have graded cortical distributions with the highest levels at the anterior and posterior poles, respectively, and the lowest levels of these proteins correlate with high LET-99 accumulation. These results suggest that PAR-3 and PAR-1 inhibit the localization of LET-99 to generate a band pattern. In addition, PAR-1 kinase activity is required for the inhibition of LET-99 localization, and PAR-1 associates with LET-99. Finally, examination of par-1 embryos suggests that the banded pattern of LET-99 is critical for normal posterior spindle displacement and to prevent spindle misorientation caused by cell shape constraints.