Hoang B, Chiba A
Department of Cell and Structural Biology, University of Illinois, Urbana, Illinois 61801, USA.
J Neurosci. 1998 Oct 1;18(19):7847-55. doi: 10.1523/JNEUROSCI.18-19-07847.1998.
Heterodimeric cell surface receptor integrin is widely expressed in the nervous system, but its specific role during axon development has not been directly tested in vivo. We show that the Drosophila nervous system expresses low levels of positron-specific (PS) integrin subunits alphaPS1, alphaPS2, and betaPS during embryonic axogenesis. Furthermore, certain subsets of neurons express higher levels of integrin mRNAs than do the rest. Null mutations in either the alphaPS1 or alphaPS2 subunit gene cause widespread axon pathfinding errors that can be rescued by supplying the wild-type integrin subunit to the mutant nervous system. In contrast, misexpressing either the alphaPS1 or alphaPS2 integrin subunit in all neurons leads to no obvious axon pathfinding errors. We propose that integrin does not itself serve as either a "clutch" constituting molecule or a specific growth cone "receptor," as proposed previously, but rather as part of a molecular network that cooperatively guarantees accurate axon guidance.
异二聚体细胞表面受体整合素在神经系统中广泛表达,但其在轴突发育过程中的具体作用尚未在体内得到直接验证。我们发现,果蝇神经系统在胚胎轴突发生过程中表达低水平的正电子特异性(PS)整合素亚基αPS1、αPS2和βPS。此外,某些神经元亚群比其他神经元表达更高水平的整合素mRNA。αPS1或αPS2亚基基因的无效突变会导致广泛的轴突寻路错误,通过向突变的神经系统提供野生型整合素亚基可以挽救这些错误。相比之下,在所有神经元中过表达αPS1或αPS2整合素亚基不会导致明显的轴突寻路错误。我们提出,整合素并不像之前所提出的那样,本身作为“离合器”构成分子或特定的生长锥“受体”,而是作为分子网络的一部分,协同保证轴突的精确导向。