Leterrier J F, Kurachi M, Tashiro T, Janmey P A
Department of Neurosciences, UMR 6187 CNRS, P.B.S., Poitiers University, 40 Avenue du, Recteur Pineau, 86022, Poitiers Cedex, France.
Eur Biophys J. 2009 Apr;38(4):381-93. doi: 10.1007/s00249-008-0381-1. Epub 2008 Nov 14.
Microtubule-associated proteins (MAPs) are involved in microtubule (MT) bundling and in crossbridges between MTs and other organelles. Previous studies have assigned the MT bundling function of MAPs to their MT-binding domain and its modulation by the projection domain. In the present work, we analyse the viscoelastic properties of MT suspensions in the presence or the absence of cAMP. The experimental data reveal the occurrence of interactions between MT polymers involving MAP2 and modulated by cAMP. Two distinct mechanisms of action of cAMP are identified, which involve on one hand the phosphorylation of MT proteins by the cAMP-dependent protein kinase A (PKA) bound to the end of the N-terminal projection of MAP2, and on the other hand the binding of cAMP to the RII subunit of the PKA affecting interactions between MTs in a phosphorylation-independent manner. These findings imply a role for the complex of PKA with the projection domain of MAP2 in MT-MT interactions and suggest that cAMP may influence directly the density and bundling of MT arrays in dendrites of neurons.
微管相关蛋白（MAPs）参与微管（MT）的成束以及微管与其他细胞器之间的交联。先前的研究已将MAPs的微管成束功能归因于其微管结合结构域及其由突出结构域介导的调节作用。在本研究中，我们分析了在有或没有cAMP的情况下微管悬浮液的粘弹性特性。实验数据揭示了涉及MAP2且受cAMP调节的微管聚合物之间相互作用的存在。确定了cAMP的两种不同作用机制，一方面涉及与MAP2 N端突出结构末端结合的cAMP依赖性蛋白激酶A（PKA）对微管蛋白的磷酸化作用，另一方面涉及cAMP与PKA的RII亚基结合，以一种不依赖磷酸化的方式影响微管之间的相互作用。这些发现表明PKA与MAP2突出结构域的复合物在微管-微管相互作用中发挥作用，并表明cAMP可能直接影响神经元树突中微管阵列的密度和成束。
