Elucidation of the mechanism of Cdc42-dependent salivary gland acinar cell formation

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K20764
• Project/Area Number (Other): 17H07212 (2017-2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2017-2018)
• Research Field: Functional basic dentistry
• Research Institution: Asahi University
• Principal Investigator: Shitara Akiko 朝日大学, 歯学部, 講師 (30508718)
• Project Period (FY): 2017-08-25 – 2020-03-31
• Keywords: 唾液腺 / 唾液腺 / 細胞内輸送 / Cdc42 / 細胞極性 / in vivoイメージング / アクチン細胞骨格

Outline of Final Research Achievements

To define the role of Cdc42 during development of salivary acinar cell, we analyzed the morphological change of acinar cell in Cdc42-depleted mouse. Depletion of Cdc42 at late embryonic stages resulted in a complete inhibition of apical membrane their post-natal formation. In addition, intravital subcellular microscopy revealed that reduced levels of Cdc42 affected membrane trafficking from and towards the plasma membrane, highlighting a novel role for Cdc42 in membrane remodeling through the negative regulation of selected endocytic pathways.
We further showed that Cdc42 depletion alters the ultrastructure of large secretory granules analyzed by transmission electron microscopy. We found that lack of Cdc42 increases the number of granules per cell and alters their structure. Specifically, granules are smaller, less circular and exhibit heterogenous electron densities in their lumen. Our findings suggest a novel role for Cdc42 in controlling granule biogenesis and/or maturation.

Free Research Field

歯科薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究では唾液腺発生の後期に始まる腺房細胞発生機構に着目し、低分子量Gタンパク質であるCdc42が細胞内輸送の制御を介して腺房細胞の腺腔側膜の形成に重要な役割を果たすことを示した。これまで障害を受けた唾液腺を再生する技術を開発するために、唾液腺の発生機構の解析が行われてきた。本研究成果は発生前期の分枝形態形成期の唾液腺を用いた従来の多くの研究と、成熟した唾液腺組織の間のギャップを埋めるものであり、この研究から唾液腺の再生療法の確立に大きく前進する「Cdc42依存性の腺房細胞の発生機構」という新規の重要なトピックが提供された。