Biochemistry II Laboratory, Department of Applied Chemistry, Faculty of Chemistry, University of The Basque Country, Manuel de Lardizabal, 3, 20018, San Sebastian, Spain.
Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040, Madrid, Spain.
Cell Mol Life Sci. 2019 Nov;76(21):4369-4390. doi: 10.1007/s00018-019-03121-5. Epub 2019 May 7.
Permanently polarized cells have developed transduction mechanisms linking polarity sites with gene regulation in the nucleus. In neurons, one mechanism is based on long-distance retrograde migration of transcription factors (TFs). Aspergillus nidulans FlbB is the only known fungal TF shown to migrate retrogradely to nuclei from the polarized region of fungal cells known as hyphae. There, FlbB controls developmental transitions by triggering the production of asexual multicellular structures. FlbB dynamics in hyphae is orchestrated by regulators FlbE and FlbD. At least three FlbE domains are involved in the acropetal transport of FlbB, with a final MyoE/actin filament-dependent step from the subapex to the apex. Experiments employing a T2A viral peptide-containing chimera (FlbE::mRFP::T2A::FlbB::GFP) suggest that apical FlbB/FlbE interaction is inhibited to initiate a dynein-dependent FlbB transport to nuclei. FlbD controls the nuclear accumulation of FlbB through a cMyb domain and a C-terminal LxxLL motif. Overall, results elucidate a highly dynamic pattern of FlbB interactions, which enable timely developmental induction. Furthermore, this system establishes a reference for TF-based long-distance signaling in permanently polarized cells.
已分化的细胞形成了将极性位点与核内基因调控联系起来的转导机制。在神经元中，一种机制基于转录因子（TF）的长距离逆行迁移。在真菌中，只有 Aspergillus nidulans FlbB 这种 TF 被证明可以从称为菌丝的真菌细胞的极化区域逆行迁移到细胞核。在那里，FlbB 通过触发无性多细胞结构的产生来控制发育转变。FlbB 在菌丝中的动态由 FlbE 和 FlbD 调节剂协调。至少有三个 FlbE 结构域参与 FlbB 的向顶运输，最后是从亚顶到顶的 MyoE/肌动蛋白丝依赖性步骤。使用含有 T2A 病毒肽的嵌合体（FlbE::mRFP::T2A::FlbB::GFP）进行的实验表明，顶端 FlbB/FlbE 相互作用被抑制，以启动依赖于动力蛋白的 FlbB 向核的运输。FlbD 通过一个 cMyb 结构域和一个 C 末端 LxxLL 基序控制 FlbB 的核积累。总的来说，结果阐明了 FlbB 相互作用的高度动态模式，这使及时的发育诱导成为可能。此外，该系统为永久性极化细胞中的基于 TF 的长距离信号提供了参考。
