Evolution and Functioning of ATP Buffering Systems at the Protist-Metazoan Interface

原生动物-后生动物界面的ATP缓冲系统的进化和功能W。佛罗里达州立大学的罗斯·艾灵顿所有的活细胞都必须以一种名为三磷酸腺苷的物质的形式产生化学能，简称三磷酸腺苷。当ATP被分解时，释放的能量为生物合成、运动和膜运输等关键的细胞过程提供动力。在某些情况下，可能会出现一过性的ATP供需错配，就像肌肉细胞爆发性收缩时一样。或者，可能存在ATP供需的空间错配，即ATP的主要来源，即被称为线粒体的小细胞内结构，在细胞层面上位于距离使用ATP的地方很远的地方。动物进化出了一种被称为磷酸根的能量储存化合物，它起到了ATP缓冲的作用。像磷酸精氨酸或磷酸肌酸一样，磷酸使ATP水平保持相对恒定，从而缓解了ATP供需的时间和空间错配。精氨酸激酶(AK)和肌酸激酶(CK)是参与上述磷酸原功能的关键代谢酶。AK和CK在肌纤维、神经元、运输上皮和原始型精子等细胞中表达。这项拟议的研究工作试图探索AK和CK在原生动物和海绵动物--最古老、现存的后生动物(多细胞动物)--界面上的早期功能作用和进化。提出了三个中心假设-(1)在后生动物起源之初，CK是从一个类似AK的祖先进化而来的；(2)在这个谱系的非常早期，CK进化成三个不同的CK基因，每个基因编码定位于细胞不同位置的独特蛋白质；(3)AK和CK都只在海绵及其原生祖先的空间ATP缓冲中发挥作用；不同的CK基因进化来促进这一作用。这项拟议的努力将坚定地确立海绵及其被认为是密切相关的原生生物盟友--脊椎动物--的磷酸原系统的早期功能作用。拟议的努力将对研究生和本科生的培训产生广泛影响，将对研究基础设施(序列、重组蛋白、抗血清)做出重大贡献，并促进关键的研究伙伴关系，其中两个是国际伙伴关系。

Evolution and Functioning of ATP Buffering Systems at the Protist-Metazoan InterfaceW. Ross Ellington, Florida State UniversityAll living cells must produce chemical energy in the form of a substance called adenosine triphosphate- ATP for short. When ATP is broken down, the energy released provides the driving force for such critical cellular processes as biosynthesis, motility and membrane transport. Under certain circumstances, there may be a temporal mismatch of ATP supply and demand as may take place during burst contraction in muscle cells. Alternatively, there may be a spatial mismatch of ATP supply and demand in which the primary sources of ATP, small intracellular structures known as mitochondria, are located large distances in cellular terms from where the ATP is used. Animals have evolved energy storage compounds known as phosphagens that act as ATP buffers. Phosphagens, like phosphoarginine or phosphocreatine, keep ATP levels relatively constant thereby mitigating temporal and spatial mismatches of ATP supply and demand. Arginine kinase (AK) and creatine kinase (CK) are key metabolic enzymes that are agents in the functioning of the above phosphagens. AK and CK are expressed in cells such as muscle fibers, neurons, transport epithelia and primitive-type spermatozoa. The proposed research effort seeks to probe the early functional roles and evolution of AK and CK at the interface of protists and sponges, the oldest, extant metazoan (multi-cellular animals) group. Three central hypotheses are posed- (1) CK evolved from an AK-like ancestor at the dawn of the origin of the metazoans; (2) very early in this lineage, CK evolved into three different CK genes, each coding for unique proteins that are localized in different places in cells; and (3) Both AK and CK function exclusively in spatial ATP buffering in sponges and their protist ancestors; the different CK genes evolved to facilitate this role. The proposed effort will firmly establish the early functional role of phosphagen systems in sponges and what are thought to be their closely related protist allies, the choanoflagellates. The proposed effort will have widespread impact on the training of graduate and undergraduate students, will make major contributions to research infrastructure (sequences, recombinant protein, anti-sera) as well as facilitate key research partnerships, two of which are international.