Spatial and temporal second messenger codes for growth cone turning
Spatial and temporal second messenger codes for growth cone turning
复制标题
DOI：
10.1073/pnas.1100247108
复制
发表时间：
2011-08-16
影响因子：
11.1
通讯作者：
Spitzer, Nicholas C.
中科院分区：
文献类型：
--
作者：
Nicol, Xavier;Hong, Kwan Pyo;Spitzer, Nicholas C.
环磷酸腺苷（cAMP）和钙是普遍存在的，相互依赖的第二信使，调节广泛的细胞过程。在神经元网络的发育过程中，它们对于回路形成的第一步至关重要，转导轴突寻路所需的信号。令人惊讶的是，轴突导向分子使用的空间和时间cAMP和钙代码是未知的。在这里，我们确定的特点，cAMP和钙瞬变产生的生长锥在Netrin-1依赖性轴突的指导。在丝状伪足中，Netrin-1依赖性结直肠癌（DCC）受体激活诱导cAMP短暂增加，导致钙瞬时频率短暂增加。相反，生长锥中心DCC的激活导致瞬时钙依赖性cAMP增加和钙瞬变频率的持续增加。我们发现，丝状伪足cAMP瞬变调节脊髓轴突的指导在体外和连合轴突在体内寻路。这些生长锥编码为特异性下游效应子的选择性激活提供了基础。
Cyclic AMP (cAMP) and calcium are ubiquitous, interdependent second messengers that regulate a wide range of cellular processes. During development of neuronal networks they are critical for the first step of circuit formation, transducing signals required for axon pathfinding. Surprisingly, the spatial and temporal cAMP and calcium codes used by axon guidance molecules are unknown. Here, we identify characteristics of cAMP and calcium transients generated in growth cones during Netrin-1-dependent axon guidance. In filopodia, Netrin-1-dependent Deleted in Colorectal Cancer (DCC) receptor activation induces a transient increase in cAMP that causes a brief increase in calcium transient frequency. In contrast, activation of DCC in growth cone centers leads to a transient calcium-dependent cAMP increase and a sustained increase in frequency of calcium transients. We show that filopodial cAMP transients regulate spinal axon guidance in vitro and commissural axon pathfinding in vivo. These growth cone codes provide a basis for selective activation of specific downstream effectors.