Establishment of Par-Polarized Cortical Domains via Phosphoregulated Membrane Motifs.
Establishment of Par-Polarized Cortical Domains via Phosphoregulated Membrane Motifs.
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DOI：
10.1016/j.devcel.2015.09.016
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发表时间：
2015-10-26
影响因子：
11.8
通讯作者：
Prehoda KE
中科院分区：
文献类型：
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作者：
Bailey MJ;Prehoda KE
PAR极性复合体在不同的动物细胞中创造了相互排斥的皮质结构域。非典型蛋白激酶C(APKC)的活性是PAR复合体的关键输出，因为磷酸化从PAR结构域中去除底物。在这里，我们研究了不同的、表面上无关的PAR底物是如何将磷酸化与皮质移位相结合的。每个蛋白质都含有一个碱性和疏水性(BH)基序，该基序直接与磷脂相互作用，并与PKC磷酸化位点重叠。磷酸化改变了序列的静电特性，抑制了与磷脂和细胞皮质的相互作用。我们在几个动物蛋白质组中寻找重叠的BH和aPKC磷酸化位点基序(即假定的磷酸化调节的BH基序)。具有强PRBH信号的候选蛋白与细胞皮质相关，但被aPKC移位到细胞质中。这些发现证明了一种潜在的一般机制，可以将蛋白质排除在极化细胞的PAR皮质区域之外。
The Par polarity complex creates mutually exclusive cortical domains in diverse animal cells. Activity of the atypical protein kinase C (aPKC) is a key output of the Par complex as phosphorylation removes substrates from the Par domain. Here we investigate how diverse, apparently unrelated Par substrates, couple phosphorylation to cortical displacement. Each protein contains a basic and hydrophobic (BH) motif that interacts directly with phospholipids and also overlaps with aPKC phosphorylation sites. Phosphorylation alters the electrostatic character of the sequence, inhibiting interaction with phospholipids and the cell cortex. We searched for overlapping BH and aPKC phosphorylation site motifs (i.e. putative PhosphoRegulated BH motifs) in several animal proteomes. Candidate proteins with strong PRBH signals associated with the cell cortex but were displaced into the cytoplasm by aPKC. These findings demonstrate a potentially general mechanism for exclusion of proteins from the Par cortical domain in polarized cells.