Tint I S, Bershadsky A D, Gelfand I M, Vasiliev J M
Department of Biological Sciences, Rutgers University, Newark, NJ 07102.
Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6318-22. doi: 10.1073/pnas.88.14.6318.
The protein kinase C activator phorbol 12-myristate 13-acetate (PMA) induces rapid and reversible shape changes in cultured fibroblasts: extension of motile lamellas is followed by transformation of these lamellas into nonmotile stalklike processes. This "lamella-to-stalk" transformation was found to be associated with the formation of microtubules enriched in detyrosinated alpha-tubulin. This change was local: microtubules in motile lamellas at the distal ends of the processes and in the cell bodies were not enriched in detyrosinated alpha-tubulin. Detyrosinated microtubules in the processes were more resistant to Colcemid treatment than other microtubules of PMA-treated and control cells. The effects of PMA were reversible and could be abolished by sphingosine, a specific inhibitor of protein kinase C. Besides modification of microtubules, lamella-to-stalk transformation is associated with the ingrowth of intermediate filaments into the extensions. Earlier it was found that this transformation is also associated with the profound reorganization of the system of actin microfilaments. Thus, all three cytoskeletal systems are altered simultaneously during PMA-induced formation of processes. Similar "cytoskeletal synergies" may play essential roles in many morphogenetic processes--e.g., in the growth of neurites.
蛋白激酶C激活剂佛波酯12 -肉豆蔻酸酯13 -乙酸酯（PMA）可诱导培养的成纤维细胞发生快速且可逆的形态变化：活动的片状伪足伸展后，这些片状伪足会转变为不活动的茎状突起。研究发现，这种“片状伪足到茎状突起”的转变与富含去酪氨酸化α -微管蛋白的微管形成有关。这种变化具有局部性：在突起远端的活动片状伪足以及细胞体中的微管，并不富含去酪氨酸化α -微管蛋白。突起中的去酪氨酸化微管比PMA处理的细胞和对照细胞的其他微管对秋水仙酰胺处理更具抗性。PMA的作用是可逆的，并且可以被蛋白激酶C的特异性抑制剂鞘氨醇消除。除了微管的修饰外，片状伪足到茎状突起的转变还与中间丝向内生长到突起中有关。早期研究发现，这种转变还与肌动蛋白微丝系统的深刻重组有关。因此，在PMA诱导的突起形成过程中，所有三种细胞骨架系统会同时发生改变。类似的“细胞骨架协同作用”可能在许多形态发生过程中发挥重要作用——例如，在神经突的生长过程中。
