Dynamin-2在神經肌肉接合處後端所扮演的角色

Abstract

Dynamin是一種大型GTP水解酶，因其在胞吞過程中催化膜分裂而聞名。有越來越多研究發現dynamin的功能並不侷限於膜上，一些需要機動蛋白重塑的位置，例如足小體、侵襲體、以及板狀偽足上都可以見到dynamin的身影。儘管過去研究發現足小體可以調節神經肌肉接合處（neuromuscular junction, NMJ）的發育，且在這些足小體上可以看到dynamin的聚集，但dynamin是否以及如何調節NMJ的發育尚不清楚。在本篇研究中，我們從分子、細胞、及個體的角度來回答這個問題。我們發現廣泛存在於不同細胞的dynamin亞型：dynamin-2，具有能被GTP水解調控的肌動蛋白綑綁能力，他能聚集在足小體周圍來調控足小體的生長與功能。在動物實驗中，我們還發現dynamin-2會影響突觸後細胞骨架以及果蠅的電生理活性。總結來說，我們的研究證實dynamin-2能透過調節肌動蛋白骨架重塑，進而促進NMJ突觸後發育。

Dynamin is a large GTPase most-known for catalyzing membrane fission during endocytosis. Growing evidence suggests that the function of dynamin is not restricted to membrane but also required at sites where endocytosis-independent actin remodeling occurs: including podosome, invadopodium, and lamellipodium. Although podosome has been shown to regulate NMJ development, and dynamin has been shown enriched at muscle podosomes. Whether and how dynamin regulates NMJ development remained unclear. In this study, we address this question from molecular, cellular, and organismal levels. We revealed that the ubiquitously expressed isoform, dynamin-2, is an actin-bundler with its activity regulated by GTP hydrolysis. It assembles around podosomes to regulate their growth, turnover, and function. On the organismal level, we uncover the impact of dynamin-2 in postsynaptic cytoskeleton and electrophysiological properties. To summarize, our study revealed a novel role of dynamin-2 in actin remodeling, which facilitates the process of postsynaptic NMJ development.