Zebrafish class 1 phosphatidylinositol transfer proteins: PITPbeta and double cone cell outer segment integrity in retina.

Zebrafish class 1 phosphatidylinositol transfer proteins: PITPbeta and double cone cell outer segment integrity in retina.
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DOI:
10.1111/j.1600-0854.2010.01085.x
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发表时间:
2010-09
期刊:
Traffic (Copenhagen, Denmark)
影响因子:
--
通讯作者:
Bankaitis VA
Bankaitis VA
中科院分区:
其他
文献类型:
--
作者:
Ile KE;Kassen S;Cao C;Vihtehlic T;Shah SD;Mousley CJ;Alb JG Jr;Huijbregts RP;Stearns GW;Brockerhoff SE;Hyde DR;Bankaitis VA

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磷脂酰肌醇转移蛋白(PITP)在酵母中协调脂质代谢与特定的膜运输途径的活动。另一方面,结构上不相关的后生动物特异性PITP(mPITP)是一类研究不足的蛋白质。目前还不清楚mPITP释放的生物活性,这些蛋白质的功能机制也不清楚。可溶性1类mPITP包括PITPα和PITPβ同种型。其中,β-同种型的特征特别差。在此,我们报告使用斑马鱼作为模型脊椎动物的1类mPITP的生物学功能的研究。斑马鱼表达PITPα和PITPβ-亚型(分别为Pitpna和Pitpnb)以及一种新的PITPβ-样亚型(Pitpng)。Pitpnb的表达在斑马鱼视网膜的双锥细胞中特别稳健。吗啉代介导的蛋白质敲低实验证明Pitpnb活性主要是发育中视网膜中双锥感光细胞外节的生物发生/维持所需的。相比之下,Pitpna活性对于早期发育计划的成功导航至关重要。这项研究报告了斑马鱼1类mPITP家族的初步描述,以及脊椎动物中PITPβ功能的首次分析。
Phosphatidylinositol transfer proteins (PITPs) in yeast coordinate lipid metabolism with the activities of specific membrane trafficking pathways. The structurally unrelated metazoan-specific 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 PITPα and PITPβ isoforms. Of these, the β-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 PITPα and PITPβ-isoforms (Pitpna and Pitpnb, respectively) and a novel PITPβ-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 PITPβ function in a vertebrate.
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