Yadav Shilpi, Williamson Jonathan K, Aronova Maria A, Prince Andrew A, Pokrovskaya Irina D, Leapman Richard D, Storrie Brian
a Department of Physiology and Biophysics , University of Arkansas for Medical Sciences , Little Rock , AR , USA.
b National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda , MD , USA.
Platelets. 2017 Jun;28(4):400-408. doi: 10.1080/09537104.2016.1235685. Epub 2016 Oct 18.
Platelets are small, anucleate cell fragments that are central to hemostasis, thrombosis, and inflammation. They are derived from megakaryocytes from which they inherit their organelles. As platelets can synthesize proteins and contain many of the enzymes of the secretory pathway, one might expect all mature human platelets to contain a stacked Golgi apparatus, the central organelle of the secretory pathway. By thin section electron microscopy, stacked membranes resembling the stacked Golgi compartment in megakaryocytes and other nucleated cells can be detected in both proplatelets and platelets. However, the incidence of such structures is low and whether each and every platelet contains such a structure remains an open question. By single-label, immunofluorescence staining, Golgi glycosyltransferases are found within each platelet and map to scattered structures. Whether these structures are positive for marker proteins from multiple Golgi subcompartments remains unknown. Here, we have applied state-of-the-art techniques to probe the organization state of the Golgi apparatus in resting human platelets. By the whole cell volume technique of serial-block-face scanning electron microscopy (SBF-SEM), we failed to observe stacked, Golgi-like structures in any of the 65 platelets scored. When antibodies directed against Golgi proteins were tested against HeLa cells, labeling was restricted to an elongated juxtanuclear ribbon characteristic of a stacked Golgi apparatus. By multi-label immunofluorescence microscopy, we found that each and every resting human platelet was positive for cis, trans, and trans Golgi network (TGN) proteins. However, in each case, the proteins were found in small puncta scattered about the platelet. At the resolution of deconvolved, widefield fluorescence microscopy, these proteins had limited tendency to map adjacent to one another. When the results of 3D structured illumination microscopy (3D SIM), a super resolution technique, were scored quantitatively, the Golgi marker proteins failed to map together indicating at the protein level considerable degeneration of the platelet Golgi apparatus relative to the layered stack as seen in the megakaryocyte. In conclusion, we suggest that these results have important implications for organelle structure/function relationships in the mature platelet and the extent to which Golgi apparatus organization is maintained in platelets. Our results suggest that Golgi proteins in circulating platelets are present within a series of scattered, separated structures. As separate elements, selective sets of Golgi enzymes or sugar nucleotides could be secreted during platelet activation. The establishment of the functional importance, if any, of these scattered structures in sequential protein modification in circulating platelets will require further research.
血小板是小型无核细胞碎片,在止血、血栓形成和炎症过程中起核心作用。它们源自巨核细胞,并从巨核细胞继承细胞器。由于血小板能够合成蛋白质并含有许多分泌途径中的酶,人们可能会认为所有成熟的人类血小板都含有堆叠的高尔基体,即分泌途径的核心细胞器。通过超薄切片电子显微镜观察,在血小板前体和血小板中都能检测到类似于巨核细胞和其他有核细胞中堆叠高尔基体区室的堆叠膜。然而,这种结构的发生率较低,而且每个血小板是否都含有这样的结构仍然是一个悬而未决的问题。通过单标记免疫荧光染色,发现高尔基体糖基转移酶存在于每个血小板中,并定位到分散的结构上。这些结构是否对来自多个高尔基体亚区室的标记蛋白呈阳性仍不清楚。在这里,我们应用了最先进的技术来探究静息人类血小板中高尔基体的组织状态。通过连续块面扫描电子显微镜(SBF-SEM)的全细胞体积技术,在我们计数的65个血小板中,没有观察到堆叠的、类似高尔基体的结构。当用针对高尔基体蛋白的抗体检测HeLa细胞时,标记仅限于堆叠高尔基体特有的细长核旁带。通过多标记免疫荧光显微镜观察,我们发现每个静息人类血小板的顺面、反面和反面高尔基体网络(TGN)蛋白均呈阳性。然而,在每种情况下,这些蛋白都存在于血小板中分散分布的小点中。在去卷积宽场荧光显微镜的分辨率下,这些蛋白彼此相邻定位的趋势有限。当对超分辨率技术三维结构光照显微镜(3D SIM)的结果进行定量分析时,高尔基体标记蛋白未能共同定位,这表明在蛋白质水平上,与巨核细胞中可见的分层堆叠相比,血小板高尔基体有相当程度的退化。总之,我们认为这些结果对成熟血小板中的细胞器结构/功能关系以及血小板中高尔基体组织的维持程度具有重要意义。我们的结果表明,循环血小板中的高尔基体蛋白存在于一系列分散、分离的结构中。作为独立的元件,在血小板激活过程中,可能会分泌出选择性的高尔基体酶或糖核苷酸。这些分散结构在循环血小板中连续蛋白质修饰中的功能重要性(如果有的话)的确立,还需要进一步研究。