Endocytosis mediated by megalin and cubilin is involved in enamel development.

IF 2 3区生物学 Q2 ANATOMY & MORPHOLOGY

Developmental Dynamics Pub Date : 2025-01-24 DOI:10.1002/dvdy.771

Aijia Wang, Yangxi Chen, Xinye Zhang, Ming Liu, Shumin Liu, Renata Kozyraki, Zhi Chen

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Abstract

Background: Endocytosis of enamel matrix proteins (EMPs) by ameloblasts is a key process in the mineralization of enamel during the maturation stage of amelogenesis. However, the relevant receptor mediating endocytosis of EMPs is still unclear. The aim of this study was to explore potential endocytic receptors involved in this process.

Results: Two endocytic receptors, megalin, and cubilin, were found to be distributed in ameloblasts of mouse incisors and molars during the secretory and maturation stages. Megalin was located at the distal end of ameloblasts during the maturation stage when proteolysis and recycling were the most active. Megalin and cubilin were also expressed in an ameloblast-lineage cell (ALC) line. The immunoelectron microscopy results showed that megalin was positively labeled on the vesicle structures of ALC, where endocytosis happened. Immunofluorescence showed that megalin and cubilin were colocalized with amelogenin, and the absorption of amelogenin was significantly reduced when megalin and cubilin were inhibited by their inhibitor, receptor-associated protein (RAP). Knockdown of megalin and cubilin with siRNA also reduced the ability of ALC to absorb amelogenin.

Conclusions: The results of this study suggest that megalin and cubilin are involved in the absorption process of ameloblasts during amelogenesis.

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牙釉质发育过程中有巨噬蛋白和巨噬蛋白介导的内吞作用。

背景：成釉细胞对釉质基质蛋白（EMPs）的内吞作用是成釉发育成熟阶段釉质矿化的关键过程。然而，介导EMPs内吞作用的相关受体尚不清楚。本研究的目的是探索参与这一过程的潜在内吞受体。结果：在小鼠门牙和磨牙成釉细胞的分泌和成熟阶段，发现了两种内吞受体meggalin和cubilin。meggalin位于成釉细胞的远端，在成熟阶段是蛋白质水解和再循环最活跃的阶段。Megalin和cubilin也在成釉细胞系（ALC）中表达。免疫电镜结果显示，在发生内吞作用的ALC的囊泡结构上，meggalin被阳性标记。免疫荧光显示，meggalin和cubilin与淀粉原蛋白共定位，当meggalin和cubilin被其抑制剂受体相关蛋白（receptor-associated protein， RAP）抑制时，淀粉原蛋白的吸收明显减少。用siRNA敲低meggalin和cubilin也降低了ALC吸收淀粉原蛋白的能力。结论：本研究结果表明，巨噬细胞苷和立方蛋白苷参与成釉细胞在成釉发育过程中的吸收过程。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Developmental Dynamics 生物-发育生物学

CiteScore

5.10

自引率

8.00%

发文量

116

审稿时长

3-8 weeks

期刊介绍： Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.

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