現(xiàn)在,，在繁忙的十字路口很少見到交警指揮交通的情景,，在我們的細(xì)胞里卻經(jīng)常上演與交警指揮交通類似的情景。德國海德爾堡歐洲分子生物學(xué)實(shí)驗(yàn)室（EMBL,，European Molecular Biology Laboratory）的科學(xué)家們已發(fā)現(xiàn),，一種Lem4蛋白指揮著細(xì)胞分裂的一個(gè)關(guān)鍵步驟，通過一邊阻止一種分子前進(jìn),，一邊放行另一種分子來實(shí)現(xiàn),，這一研究發(fā)表在7月6日的Cell上。
對于胚胎生長或組織再生來說,，細(xì)胞就必須進(jìn)行分裂,。當(dāng)一個(gè)細(xì)胞分裂成2個(gè)時(shí)，一旦染色體也被一分為二,，包圍細(xì)胞核的核膜就不得不瓦解,，再重建。因?yàn)榘l(fā)生這種重組,，一個(gè)BAF蛋白就必須去除磷酸化學(xué)標(biāo)簽,。蛋白質(zhì)磷酸化狀態(tài)的變化，即有或無磷酸鹽標(biāo)簽,，能涉及蛋白質(zhì)磷酸化或/和去磷酸化活性的調(diào)節(jié),。EMBL的科學(xué)家們發(fā)現(xiàn)了一種名為Lem4的新分子，它擔(dān)任著交警的角色,，一邊阻止一個(gè)蛋白給BAF加磷酸化標(biāo)簽,，一邊又讓另一個(gè)蛋白質(zhì)去除已有標(biāo)簽。
這也發(fā)生在人類細(xì)胞和秀麗隱桿線蟲（C. elegans）中,，它似乎是一種進(jìn)化很久的策略,。通過遺傳學(xué)與生物化學(xué)的結(jié)合研究，科學(xué)家們發(fā)現(xiàn)即使線蟲版Lem4與人類版的完全不同,，但在細(xì)胞分裂結(jié)束時(shí),，它們都執(zhí)行相同的雙重任務(wù)。這種單一分子既阻止標(biāo)簽添加又促進(jìn)標(biāo)簽去除的策略,，可能用于許多涉及磷酸化標(biāo)簽的細(xì)胞過程中,，如細(xì)胞生長和分裂、環(huán)境信號(hào)傳入細(xì)胞,。那么,，又是什么激發(fā)Lem4在恰當(dāng)?shù)臅r(shí)候開始雙重行動(dòng)了？這正是科學(xué)家們接下來要研究的內(nèi)容,。（生物谷bioon.com）
doi:10.1016/j.cell.2012.04.043
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PMID:
Coordination of Kinase and Phosphatase Activities by Lem4 Enables Nuclear Envelope Reassembly during Mitosis
Claudio Asencio, Iain F. Davidson, Rachel Santarella-Mellwig, Thi Bach Nga Ly-Hartig, Moritz Mall, Matthew R. Wallenfang, Iain W. Mattaj, Mátyás Gorjánácz
Mitosis in metazoa requires nuclear envelope (NE) disassembly and reassembly. NE disassembly is driven by multiple phosphorylation events. Mitotic phosphorylation of the protein BAF reduces its affinity for chromatin and the LEM family of inner nuclear membrane proteins; loss of this BAF-mediated chromatin-NE link contributes to NE disassembly. BAF must reassociate with chromatin and LEM proteins at mitotic exit to reform the NE; however, how its dephosphorylation is regulated is unknown. Here, we show that the C. elegans protein LEM-4L and its human ortholog Lem4 (also called ANKLE2) are both required for BAF dephosphorylation. They act in part by inhibiting BAF's mitotic kinase, VRK-1, in vivo and in vitro. In addition, Lem4/LEM-4L interacts with PP2A and is required for it to dephosphorylate BAF during mitotic exit. By coordinating VRK-1- and PP2A-mediated signaling on BAF, Lem4/LEM-4L controls postmitotic NE formation in a function conserved from worms to humans.
