Phylogenetic Analysis of the NEEP21/Calcyon/P19 Family of Endocytic Proteins: Evidence for Functional Evolution in the Vertebrate CNS
Phylogenetic Analysis of the NEEP21/Calcyon/P19 Family of Endocytic Proteins: Evidence for Functional Evolution in the Vertebrate CNS
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DOI：
10.1007/s00239-009-9273-y
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发表时间：
2009-10-01
影响因子：
3.9
通讯作者：
Bergson, Clare
中科院分区：
文献类型：
--
作者：
Muthusamy, Nagendran;Ahmed, Sanaa A.;Bergson, Clare
内吞作用和囊泡运输是最佳神经传递所必需的。然而，目前对调节这些过程的神经元蛋白的进化知之甚少。在这里，我们报告的NEEP 21，calcyon，和P19，一个家庭的神经元蛋白牵连在突触受体内吞和回收，以及在膜蛋白贩运的体树突和轴突车厢分化的神经元的第一个系统发育研究。数据库检索确定了P19和NEEP 21在硬骨鱼中的直系同源物，但没有尾索动物或无脊椎动物门。钙尾鱼的直系同源物仅从哺乳动物数据库和硬骨鱼的远亲中检索。原位定位的P19斑马鱼直系同源物，和现存的祖先的基因家族，揭示了中枢神经系统的特异性表达模式。基于非同义核苷酸取代率，钙蛋白基因似乎处于较低强度的负选择压力下。事实上，功能组II WW结构域结合基序在灵长类动物和人类钙蛋白中检测到，但在非灵长类动物直系同源物中未检测到。从80人受试者的calcyon基因的测序揭示了一个非同义的单核苷酸多态性，废除组II WW结构域蛋白结合。总之，我们的数据表明，NEEP 21/calcyon/P19基因家族出现，并经历了两轮基因复制相对较晚的后生动物进化（但早期的脊椎动物进化最晚）。由于功能研究表明NEEP 21和钙蛋白在调节突触和神经元的囊泡运输中发挥相关但不同的作用，我们建议该家族出现在脊索动物中，以支持更多样化的突触和行为反应。
Endocytosis and vesicle trafficking are required for optimal neural transmission. Yet, little is currently known about the evolution of neuronal proteins regulating these processes. Here, we report the first phylogenetic study of NEEP21, calcyon, and P19, a family of neuronal proteins implicated in synaptic receptor endocytosis and recycling, as well as in membrane protein trafficking in the somatodendritic and axonal compartments of differentiated neurons. Database searches identified orthologs for P19 and NEEP21 in bony fish, but not urochordate or invertebrate phyla. Calcyon orthologs were only retrieved from mammalian databases and distant relatives from teleost fish. In situ localization of the P19 zebrafish ortholog, and extant progenitor of the gene family, revealed a CNS specific expression pattern. Based on non-synonymous nucleotide substitution rates, the calcyon genes appear to be under less intense negative selective pressure. Indeed, a functional group II WW domain binding motif was detected in primate and human calcyon, but not in non-primate orthologs. Sequencing of the calcyon gene from 80 human subjects revealed a non-synonymous single nucleotide polymorphism that abrogated group II WW domain protein binding. Altogether, our data indicate the NEEP21/calcyon/P19 gene family emerged, and underwent two rounds of gene duplication relatively late in metazoan evolution (but early in vertebrate evolution at the latest). As functional studies suggest NEEP21 and calcyon play related, but distinct roles in regulating vesicle trafficking at synapses, and in neurons in general, we propose the family arose in chordates to support a more diverse range of synaptic and behavioral responses.