Zoological Institute, University of Braunschweig, Germany.
Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15780-5. doi: 10.1073/pnas.1004406107. Epub 2010 Aug 23.
Two profilin isoforms (PFN1 and PFN2a) are expressed in the mammalian brain. Although profilins are essential for regulating actin dynamics in general, the specific role of these isoforms in neurons has remained elusive. We show that knockdown of the neuron-specific PFN2a results in a significant reduction in dendrite complexity and spine numbers of hippocampal neurons. Overexpression of PFN1 in PFN2a-deficient neurons prevents the loss of spines but does not restore dendritic complexity. Furthermore, we show that profilins are involved in differentially regulating actin dynamics downstream of the pan-neurotrophin receptor (p75(NTR)), a receptor engaged in modulating neuronal morphology. Overexpression of PFN2a restores the morphological changes in dendrites caused by p75(NTR) overexpression, whereas PFN1 restores the normal spine density. Our data assign specific functions to the two PFN isoforms, possibly attributable to different affinities for potent effectors also involved in actin dynamics, and suggest that they are important for the signal-dependent fine-tuning of neuronal architecture.
两种丝切蛋白同工型（PFN1 和 PFN2a）在哺乳动物大脑中表达。尽管丝切蛋白普遍参与调节肌动蛋白动力学，但这些同工型在神经元中的具体作用仍难以捉摸。我们发现，神经元特异性 PFN2a 的敲低导致海马神经元树突复杂性和棘突数量显著减少。在 PFN2a 缺陷神经元中过表达 PFN1 可以防止棘突丢失，但不能恢复树突复杂性。此外，我们发现丝切蛋白参与调节泛神经生长因子受体（p75（NTR））下游的肌动蛋白动力学，该受体参与调节神经元形态。PFN2a 的过表达恢复了 p75（NTR）过表达引起的树突形态变化，而 PFN1 则恢复了正常的棘突密度。我们的数据为这两种 PFN 同工型赋予了特定的功能，这可能归因于它们与参与肌动蛋白动力学的强效效应物的不同亲和力，并表明它们对于信号依赖性神经元结构的精细调节很重要。
