在一項(xiàng)新研究中，研究人員報(bào)道幫助洗液軟化皮膚的脂質(zhì)也幫助細(xì)胞發(fā)現(xiàn)和停留在體內(nèi)正確位置以確保它們的“觸角(antennae)”向上,。相關(guān)研究結(jié)果于2012年6月20日發(fā)表在Molecular Biology of the Cell 期刊上,。
研究通訊作者、美國(guó)佐治亞健康科學(xué)大學(xué)佐治亞醫(yī)學(xué)院生物學(xué)學(xué)家Erhard Bieberich博士說(shuō),，每個(gè)細(xì)胞都有“觸角”或者說(shuō)纖毛,，這種纖毛能夠感知環(huán)境，從而確定細(xì)胞去哪里以及當(dāng)它達(dá)到時(shí)做什么,。
Bieberich說(shuō),，細(xì)胞需要一種細(xì)胞器來(lái)感知它所在的位置以便它前往它想要和需要去的地方。
他的研究小組證實(shí)脂質(zhì)神經(jīng)酰胺(ceramide)通過(guò)抑制組蛋白去乙酰酶6(histone deacetylase 6, HDAC6)幫助細(xì)胞阻止這種細(xì)胞器或者說(shuō)纖毛縮回,。
當(dāng)發(fā)生細(xì)胞分裂時(shí),，纖毛必須縮回，而且激活HDAC6使得這種縮回在某些情況下是必需的，比如藥物開(kāi)發(fā)或者當(dāng)需要更多的皮膚細(xì)胞或胃腸道細(xì)胞替換正常的周轉(zhuǎn)時(shí),。Bieberich說(shuō),，有趣的是，癌細(xì)胞是分裂速度最快的一些細(xì)胞,，并且“濫用”HDAC來(lái)實(shí)現(xiàn)這點(diǎn)的,；它們也抑制神經(jīng)酰胺，這是因?yàn)橐阎窠?jīng)酰胺誘導(dǎo)細(xì)胞自殺,。
神經(jīng)酰胺實(shí)際上確實(shí)是一個(gè)多面手(multi-tasker),。Bieberich研究小組在2007年在Journal of Biological Chemistry期刊上報(bào)道在發(fā)育最為初始的期間，它有幫助定位干細(xì)胞以便確定哪個(gè)方向向上和找到它們所在的正確位置,，而且這種位置對(duì)于胚胎產(chǎn)生比較重要,。而在2004年，研究人員發(fā)現(xiàn)脂質(zhì)神經(jīng)酰胺與蛋白PAR-4相互協(xié)作來(lái)清除發(fā)育中大腦內(nèi)的無(wú)用細(xì)胞,。(生物谷：Bioon.com)
本文編譯自Lipid helps cells find their way by keeping their 'antennae' up
doi:10.1091/mbc.E12-02-0079
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Characterizationtr of an apical ceramide-enriched compartment (ACEC) regulating ciliogenesis
Qian He, Guanghu Wang, Somsankar Dasgupta, Michael Dinkins, Gu Zhu, and Erhard Bieberich
We show here that in MDCK cells, an apical ceramide-enriched compartment (ACEC) at the base of primary cilia is colocalized with Rab11a. Ceramide and Rab11a vesicles isolated by magnetic sorting contain a highly similar profile of proteins (aPKC, Cdc42, Sec8, Rab11a and Rab8) and ceramide species, suggesting the presence of a ciliogenic protein complex associated with ceramide at the ACEC. Intriguingly, C16 and C18 ceramide, although less abundant ceramide species in MDCK cells, are highly enriched in ceramide and Rab11a vesicles. Expression of a ceramide binding but dominant negative mutant of aPKC suppresses ciliogenesis, indicating that the association of ceramide with aPKC is critical for the formation of this complex. Our results indicate that ciliogenic ceramide is derived from apical sphingomyelin (SM) that is endocytosed and then converted to the ACEC. Consistently, inhibition of acid sphingomyelinase with imipramine disrupts ACEC formation, association of ciliogenic proteins with Rab11a vesicles, and cilium formation. Ciliogenesis is rescued by the histone deacetylase inhibitor trichostatin A, indicating that ceramide promotes tubulin acetylation in cilia. Taken together, our results suggest that the ACEC is a novel compartment in which SM-derived ceramide induces formation of a ciliogenic lipid-protein complex that sustains primary cilia by preventing deacetylation of microtubules.
