朊病毒蛋白作为神经元的反式相互作用伴侣，参与神经突生长和神经元存活。

Prion protein as trans-interacting partner for neurons is involved in neurite outgrowth and neuronal survival.

作者信息

Chen Suzhen, Mangé Alain, Dong Ling, Lehmann Sylvain, Schachner Melitta

机构信息

Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, D-20246, Hamburg, Germany

出版信息

Mol Cell Neurosci. 2003 Feb;22(2):227-33. doi: 10.1016/s1044-7431(02)00014-3.

DOI:10.1016/s1044-7431(02)00014-3

PMID:12676532

Abstract

Many uncertainties remain regarding the physiological function of the prion protein PrP and the consequences of its conversion into the pathological scrapie isoform in prion diseases. Here, we show for the first time that different signal transduction pathways are involved in neurite outgrowth and neuronal survival elicited by PrP in cell culture of primary neurons. These pathways include the nonreceptor Src-related family member p59(Fyn), PI3 kinase/Akt, cAMP-dependent protein kinase A, and MAP kinase. Regulation of Bcl-2 and Bax expression also correlates with the survival effect elicited by PrP. The combined results, along with our observation that PrP carries the recognition molecule-related HNK-1 carbohydrate, argue strongly for a role of the molecule in neural recognition by interacting with yet unknown heterophilic neuronal receptors, as shown by comparison of neurite outgrowth from neurons of PrP-deficient and wild-type mice.

摘要

关于朊病毒蛋白PrP的生理功能及其在朊病毒疾病中转化为病理性瘙痒病异构体的后果，仍存在许多不确定性。在此，我们首次表明，在原代神经元细胞培养中，不同的信号转导途径参与了由PrP引发的神经突生长和神经元存活。这些途径包括非受体Src相关家族成员p59(Fyn)、PI3激酶/Akt、cAMP依赖性蛋白激酶A和MAP激酶。Bcl-2和Bax表达的调节也与PrP引发的存活效应相关。综合这些结果，以及我们观察到PrP携带与识别分子相关的HNK-1碳水化合物，通过比较PrP缺陷型和野生型小鼠神经元的神经突生长，有力地证明了该分子通过与未知的嗜异性神经元受体相互作用在神经识别中发挥作用。