果蠅蛋白質酪胺酸去磷酸酶dPTPmeg在神經肌肉接合處的發育上所扮演角色

Abstract

蛋白質酪胺酸去磷酸酶 (protein tyrosine phosphatases；PTPs)與蛋白質酪胺酸磷酸酶 (Protein tyrosine kinases) 參與在細胞中許多發育生長的過程。在果蠅的研究中發現有許多的受器型蛋白質酪胺酸去磷酸酶有參與在神經肌肉接合處(neuromuscular junction ,NMJ)的發育，如 dLAR、dPTP69D 以及 dPTP99A。但有關於非受器型蛋白質酪胺酸去磷酸酶(non-transmembrane PTPs；NTPTPs)在神經肌肉接合處發育上扮演的角色仍然不清楚。近期研究報導指出，果蠅其中一個非受器型蛋白質酪胺酸去磷酸酶，dPTPMmeg，對於其腦部蕈狀體(mushroom body)軸突伸展(axon projection)的建立是必須的。在本論文中，我們主要研究dPTPmeg 在神經肌肉接合處所扮演的角色。我們發現，當 dPTPmeg 過度表現時會使得果蠅神經肌肉接合處的 type Ib bouton 數量減少，但是在 dPTPmeg 基因突變的果蠅中我們並沒有看在神經肌肉接合處發育上有的明顯地缺陷。我們進一步發現 Src 是 dPTPmeg 交互作用的蛋白質，先前報導已發現 Src 對於神經肌肉接合處的發育非常重要，基因遺傳分析的資料顯示，Src 表現下降能夠些微地恢復dPTPmeg 所造成的缺陷。因此，對於正常地神經肌肉交界處的發育來說， dPTPmeg與 Src 之間的交互作用是很重要的。

Protein tyrosine phosphatases (PTPs) are involved in the coordination of protein tyrosine kinases in various cellular processes. In Drosophila, many receptor-like protein tyrosine phosphatases(RPTPs), such as dLAR dPTP69D, and dPTP99A, are required for the development of neuromuscular junction (NMJ) but the role of non-transmembrane protein tyrosine phosphatases (NTPTPs) in NMJ development remains unknown. Recent studies have shown that one of Drosophila NTPTPs, dPTPmeg, is required for the axon projection establishment of the mushroom body. Here we studied the role of dPTPmeg in NMJ development. Gain-of-function analysis showed that dPTPmeg decreased the type Ib bouton numbers at Drosophila NMJ. However, dPTPmeg mutant does not cause obvious defects in NMJ development. We further identified Src as a dPTPmeg interacting protein. Drosophila Src has been shown to play a role in NMJ development. Genetic analysis revealed that Src knockdown could partially rescue dPTPmeg-induced NMJ defects. These findings suggest that Drosophila PTPmeg associate with Src in the regulation of NMJ development.