生物谷报道：瑞典乌普萨拉大学的Mitch Dushay和同事在6月13日在线版PLoS ONE上的发表了一篇题为“果蝇lamin突变显性特征和人类核纤层蛋白综合征（laminopathies）的比较”文章。
Lamins是中间纤丝蛋白，它们构成了核膜下的基质。哺乳动物有两种类型的lamin蛋白：A型lamins在处于分化中的细胞中表达，而B型lamins则广泛表达。编码人类A型lamin的基因的突变会导致核纤层蛋白综合征（laminopathies），包括肌肉营养不良和早老等疾病。
黑腹果蝇有两个lamin基因，也分为A和B型，并被认为所行使的功能与人类的相似。
但是，Dushay和同事证实，果蝇lamin基因与哺乳动物lamin基因非常相似。尽管相似表达模式的独立进化必定是由相似的关键lamin基因功能所驱动，但是研究人员发现广泛表达的果蝇lamin基因的突变导致幼虫运动量更少，并且出现轻微的肌肉缺陷。
这些发现意味着lamin突变可能导致神经肌肉缺陷、早老。果蝇lamin显型和人类核纤层蛋白综合征的相似性为基因表达和进化过程中的功能分歧提供了一个有趣的例子，并且促进人们更深入地了解lamin功能以及核纤层蛋白综合征和衰老。
核纤层蛋白综合征（laminopathies）主要是指由LMNA基因及其编码蛋白laminA/C异常引起的一组人类遗传病。根据临床特征不同，至今被认识的核纤层蛋白病已有10种，除其中一种由影响成熟laminA形成的FACE-1基因突变引起外，其余9种均由LMNA基因突变引起，其中包括2种既可以常染色体显性又可以常染色体隐性遗传的遗传病：Emery-Dreifuss肌营养不良2型和3型（常显EDMD2，常隐EDMD3）和腓骨肌萎缩症2型（常显AD-CMT2，常隐AR-CMT2）；6种常染色体显性遗传病：肢带型肌营养不良1B（LGMD1B），扩张性心肌病伴心脏传导阻滞1A（CMD1A），家族部分性脂肪营养不良（FPLD），脂营养不良、胰岛素抵抗型糖尿病、弥漫性白黑皮病样丘疹、肝脂肪变性和心肌病综合征（LDHPC），Werner综合征（WRN）和早老症（HGPS）；1种常染色体隐性遗传病：Mandibuloacral dysplasia（MAD）。
原始出处:
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.
全文链接：
