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

原生生物-后生动物界面 ATP 缓冲系统的进化和功能

• 批准号: 0542236
• 负责人: W. Ross Ellington
• 金额: $ 47.43万
• 依托单位: Florida State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0542236&HistoricalAwards=false
• 关键词: Evolution; Functioning; ATP; Buffering; Systems

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.

原生动物-后生动物界面ATP缓冲系统的进化和功能。罗斯·艾灵顿，佛罗里达州立大学所有活细胞都必须以一种叫做三磷酸腺苷（简称ATP）的物质的形式产生化学能。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细胞过程提供驱动力。在某些情况下，可能存在ATP供应和需求的时间失配，如可能在肌肉细胞的爆发性收缩期间发生的。或者，可能存在ATP供给和需求的空间错配，其中ATP的主要来源，称为线粒体的小细胞内结构，在细胞方面与ATP使用的地方相距很远。动物已经进化出一种叫做磷酸盐的能量储存化合物，它可以作为ATP的缓冲剂。磷脂，如磷酸精氨酸或磷酸肌酸，保持ATP水平相对恒定，从而减轻ATP供应和需求的时间和空间错配。精氨酸激酶（AK）和肌酸激酶（CK）是关键的代谢酶，是上述磷酸酶发挥功能的试剂。AK和CK表达于肌纤维、神经元、运输上皮细胞和精子等细胞中。拟议的研究工作旨在探索早期的功能作用和进化的AK和CK的原生生物和海绵，最古老的，现存的后生动物（多细胞动物）组的接口。本文提出了三个中心假说：（1）CK是在后生动物起源之初从一个类似AK的祖先进化而来的;（2）在这一谱系的早期，CK进化成三个不同的CK基因，每个基因编码的蛋白质定位在细胞的不同位置;（3）在海绵及其原生动物祖先中，AK和CK都只起空间ATP缓冲作用;不同的CK基因进化以促进这一作用。这项提议的努力将牢固地建立起海绵中磷酸原系统的早期功能作用，以及被认为是它们密切相关的原生生物盟友--领鞭毛虫。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，其中两个是国际性的。