生物谷報道：瑞典烏普薩拉大學的Mitch Dushay和同事在6月13日在線版PLoS ONE上的發(fā)表了一篇題為“果蠅lamin突變顯性特征和人類核纖層蛋白綜合征（laminopathies）的比較”文章,。
Lamins是中間纖絲蛋白,，它們構(gòu)成了核膜下的基質(zhì),。哺乳動物有兩種類型的lamin蛋白：A型lamins在處于分化中的細胞中表達,，而B型lamins則廣泛表達。編碼人類A型lamin的基因的突變會導致核纖層蛋白綜合征（laminopathies）,，包括肌肉營養(yǎng)不良和早老等疾病,。
黑腹果蠅有兩個lamin基因，也分為A和B型,，并被認為所行使的功能與人類的相似,。
但是，Dushay和同事證實,，果蠅lamin基因與哺乳動物lamin基因非常相似,。盡管相似表達模式的獨立進化必定是由相似的關(guān)鍵lamin基因功能所驅(qū)動，但是研究人員發(fā)現(xiàn)廣泛表達的果蠅lamin基因的突變導致幼蟲運動量更少,，并且出現(xiàn)輕微的肌肉缺陷,。
這些發(fā)現(xiàn)意味著lamin突變可能導致神經(jīng)肌肉缺陷、早老,。果蠅lamin顯型和人類核纖層蛋白綜合征的相似性為基因表達和進化過程中的功能分歧提供了一個有趣的例子,，并且促進人們更深入地了解lamin功能以及核纖層蛋白綜合征和衰老。
核纖層蛋白綜合征（laminopathies）主要是指由LMNA基因及其編碼蛋白laminA/C異常引起的一組人類遺傳病,。根據(jù)臨床特征不同，至今被認識的核纖層蛋白病已有10種,，除其中一種由影響成熟laminA形成的FACE-1基因突變引起外,，其余9種均由LMNA基因突變引起，其中包括2種既可以常染色體顯性又可以常染色體隱性遺傳的遺傳?。篍mery-Dreifuss肌營養(yǎng)不良2型和3型（常顯EDMD2,，常隱EDMD3）和腓骨肌萎縮癥2型（常顯AD-CMT2，常隱AR-CMT2）,；6種常染色體顯性遺傳?。褐珟图I養(yǎng)不良1B（LGMD1B），擴張性心肌病伴心臟傳導阻滯1A（CMD1A）,，家族部分性脂肪營養(yǎng)不良（FPLD）,，脂營養(yǎng)不良、胰島素抵抗型糖尿病,、彌漫性白黑皮病樣丘疹,、肝脂肪變性和心肌病綜合征（LDHPC），Werner綜合征（WRN）和早老癥（HGPS）,；1種常染色體隱性遺傳?。篗andibuloacral dysplasia（MAD）,。
原始出處:
Characterization of lamin Mutation Phenotypes in Drosophila and Comparison to Human Laminopathies
Andrés Muñoz-Alarcón1,2, Maja Pavlovic1,2, Jasmine Wismar3, Bertram Schmitt3, Maria Eriksson2, Per Kylsten1, Mitchell S. Dushay1,4¤*
1 Department of Life Sciences, Södertörns högskola, Huddinge, Sweden, 2 Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden, 3 Max-Planck-Institut für Hirnforschung, Abteilung Neurochemie, Frankfurt, Germany, 4 Department of Comparative Physiology, EBC, Uppsala University, Uppsala, Sweden
Lamins are intermediate filament proteins that make up the nuclear lamina, a matrix underlying the nuclear membrane in all metazoan cells that is important for nuclear form and function. Vertebrate A-type lamins are expressed in differentiating cells, while B-type lamins are expressed ubiquitously. Drosophila has two lamin genes that are expressed in A- and B-type patterns, and it is assumed that similarly expressed lamins perform similar functions. However, Drosophila and vertebrate lamins are not orthologous, and their expression patterns evolved independently. It is therefore of interest to examine the effects of mutations in lamin genes. Mutations in the mammalian lamin A/C gene cause a range of diseases, collectively called laminopathies, that include muscular dystrophies and premature aging disorders. We compared the sequences of lamin genes from different species, and we have characterized larval and adult phenotypes in Drosophila bearing mutations in the lam gene that is expressed in the B-type pattern. Larvae move less and show subtle muscle defects, and surviving lam adults are flightless and walk like aged wild-type flies, suggesting that lam phenotypes might result from neuromuscular defects, premature aging, or both. The resemblance of Drosophila lam phenotypes to human laminopathies suggests that some lamin functions may be performed by differently expressed genes in flies and mammals. Such still-unknown functions thus would not be dependent on lamin gene expression pattern, suggesting the presence of other lamin functions that are expression dependent. Our results illustrate a complex interplay between lamin gene expression and function through evolution.
Figure 1. Comparison of lamin genes from different organisms.
(A) Schematic diagram of a general lamin protein showing the central rod and IF-tail domains used in sequence comparisons. (B) Condensed cladograms showing the evolutionary relationship of 28 lamin genes, compared for the central rod domain, the IF-tail domain and full protein sequences. Protostome and deuterostome sequences group together rather than with different deuterostomic lamin groups. Note also how the central rod domain of the single C elegans lamin gene is equally related to deuterostome and protosome sequences, whereas its IF-tail domain groups with other protostomal sequences. The full C. elegans lamin sequence also occupies an intermediary position. Arrows indicate the root node of respective C.elegans sequences. Bootstrap values (1000 trials) are given as percent figures near nodes. See Materials and Methods for lamin designations, and Supplemental Figure S1 for full cladograms. Sequence alignments upon which these were based are available on request.
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