Chen Xutong, Ando Ryo, Casco-Robles Roman Martin, Casco-Robles Martin Miguel, Maruo Fumiaki, Obata Shuichi, Chiba Chikafumi
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba 305-8572, Ibaraki, Japan.
Graduate School of Science and Technology, University of Tsukuba, Tennodai 1-1-1, Tsukuba 305-8572, Ibaraki, Japan.
Biomedicines. 2022 Nov 1;10(11):2772. doi: 10.3390/biomedicines10112772.
In adult newts, when a limb is amputated, a mesenchymal cell mass called the blastema is formed on the stump, where blood vessels filled with premature erythrocytes, named polychromatic normoblasts (PcNobs), elongate. We previously demonstrated that PcNobs in the blastema express an orphan gene, , and that they secrete growth factors such as BMP2 and TGFβ1 into the surrounding tissues. However, the relationship between Newtic1 expression and growth factor secretion was not clear since was thought to encode a membrane protein. In this study, we addressed this issue using morphological techniques and found that the Newtic1 protein is a component of globular structures that accumulate at the marginal band in the cytoplasm along the equator of PcNobs. Newtic1-positive (Newtic1(+)) globular structures along the equator were found only in PcNobs with a well-developed marginal band in the blastema. Newtic1(+) globular structures were associated with microtubules and potentially incorporated TGFβ1. Based on these observations, we propose a hypothesis that the Newtic1 protein localizes to the membrane of secretory vesicles that primarily carry TGFβ1 and binds to microtubules, thereby tethering secretory vesicles to microtubules and transporting them to the cell periphery as the marginal band develops.
在成年蝾螈中，当肢体被截断时，残端会形成一种称为芽基的间充质细胞团，充满早熟红细胞（称为多染性成红细胞，PcNobs）的血管在芽基处伸长。我们之前证明，芽基中的PcNobs表达一个孤儿基因Newtic1，并且它们向周围组织分泌诸如BMP2和TGFβ1等生长因子。然而，由于Newtic1被认为编码一种膜蛋白，所以Newtic1表达与生长因子分泌之间的关系尚不清楚。在本研究中，我们使用形态学技术解决了这个问题，发现Newtic1蛋白是球状结构的一个组成部分，这些球状结构沿着PcNobs赤道处的细胞质边缘带聚集。仅在芽基中边缘带发育良好的PcNobs赤道处发现了Newtic1阳性（Newtic1(+)）球状结构。Newtic1(+)球状结构与微管相关联，并可能结合TGFβ1。基于这些观察结果，我们提出一个假设，即Newtic1蛋白定位于主要携带TGFβ1的分泌囊泡膜上，并与微管结合，从而将分泌囊泡拴系到微管上，并随着边缘带的发育将它们运输到细胞周边。
