Department of Cell & Developmental Biology, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Traffic. 2010 Sep;11(9):1151-67. doi: 10.1111/j.1600-0854.2010.01085.x. Epub 2010 Jun 2.
Phosphatidylinositol transfer proteins (PITPs) in yeast co-ordinate lipid metabolism with the activities of specific membrane trafficking pathways. The structurally unrelated metazoan PITPs (mPITPs), on the other hand, are an under-investigated class of proteins. It remains unclear what biological activities mPITPs discharge, and the mechanisms by which these proteins function are also not understood. The soluble class 1 mPITPs include the PITPalpha and PITPbeta isoforms. Of these, the beta-isoforms are particularly poorly characterized. Herein, we report the use of zebrafish as a model vertebrate for the study of class 1 mPITP biological function. Zebrafish express PITPalpha and PITPbeta-isoforms (Pitpna and Pitpnb, respectively) and a novel PITPbeta-like isoform (Pitpng). Pitpnb expression is particularly robust in double cone cells of the zebrafish retina. Morpholino-mediated protein knockdown experiments demonstrate Pitpnb activity is primarily required for biogenesis/maintenance of the double cone photoreceptor cell outer segments in the developing retina. By contrast, Pitpna activity is essential for successful navigation of early developmental programs. This study reports the initial description of the zebrafish class 1 mPITP family, and the first analysis of PITPbeta function in a vertebrate.
磷脂酰肌醇转移蛋白（PITPs）在酵母中与特定膜运输途径的活性协同调节脂质代谢。另一方面，结构上不相关的后生动物 PITPs（mPITPs）是一类研究不足的蛋白质。目前尚不清楚 mPITPs 发挥什么生物学活性，也不清楚这些蛋白质的作用机制。可溶性 1 类 mPITPs 包括 PITPalpha 和 PITPbeta 同工型。其中，beta-同工型的特征尤其不明显。在此，我们报告使用斑马鱼作为研究 1 类 mPITP 生物学功能的模式脊椎动物。斑马鱼表达 PITPalpha 和 PITPbeta-同工型（分别为 Pitpna 和 Pitpnb）和一种新型 PITPbeta 样同工型（Pitpng）。Pitpnb 在斑马鱼视网膜的双圆锥细胞中表达尤为强烈。基于 Morpholino 的蛋白敲低实验表明，Pitpnb 的活性主要是双圆锥光感受器细胞外节在发育中的视网膜中发生和维持所必需的。相比之下，Pitpna 的活性对于早期发育程序的成功导航是必不可少的。本研究首次描述了斑马鱼 1 类 mPITP 家族，并首次分析了 PITPbeta 在脊椎动物中的功能。
