Guillemin K, Williams T, Krasnow M A
Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5307, USA.
Nat Cell Biol. 2001 Sep;3(9):848-51. doi: 10.1038/ncb0901-848.
Nuclear lamins are intermediate filaments that compose the nuclear lamina--the filamentous meshwork underlying the inner nuclear membrane--and are required for nuclear assembly, organization and maintenance. Here we present evidence that a nuclear lamin is also required for cytoplasmic organization in two highly polarized cell types. Zygotic loss-of-function mutations in the Drosophila gene encoding the principal lamin (Dm(0)) disrupt the directed outgrowth of cytoplasmic extensions from terminal cells of the tracheal system. Germline mutant clones disrupt dorsal-ventral polarity of the oocyte. In mutant oocytes, transcripts of the dorsal determinant Gurken, a transforming growth factor-alpha homologue, fail to localize properly around the anterodorsal surface of the oocyte nucleus; their ventral spread results in dorsalized eggs that resemble those of the classical dorsalizing mutations squid and fs(1)K10. The requirement of a nuclear lamin for cytoplasmic as well as nuclear organization has important implications for both the cellular functions of lamins and the pathogenesis of human diseases caused by lamin mutations.
核纤层蛋白是构成核纤层的中间丝，核纤层是内核膜下方的丝状网络，对于细胞核的组装、组织和维持至关重要。在此，我们提供证据表明，在两种高度极化的细胞类型中，核纤层蛋白对于细胞质组织也是必需的。果蝇中编码主要核纤层蛋白（Dm(0)）的基因发生合子功能丧失突变，会破坏气管系统终末细胞细胞质延伸的定向生长。生殖系突变克隆会破坏卵母细胞的背腹极性。在突变的卵母细胞中，背侧决定因子Gurken（一种转化生长因子-α同源物）的转录本无法正确定位在卵母细胞核前背表面周围；它们向腹侧扩散导致卵背化，类似于经典背化突变squid和fs(1)K10所产生的卵。核纤层蛋白对于细胞质和细胞核组织的需求，对于核纤层蛋白的细胞功能以及由核纤层蛋白突变引起的人类疾病的发病机制都具有重要意义。
