The function of ECM-induced assembly of podosome-like structures in the formation and remodeling of AChR clusters at neuromuscular synapses

Professor Chan Barbara Pui   (Co-Investigator)

Professor Zhou Zhongjun   (Co-Investigator)

42

2019-01-01

2022-06-30

861077

The function of ECM-induced assembly of podosome-like structures in the formation and remodeling of AChR clusters at neuromuscular synapses

Acetylcholine receptor, Extracellular matrix, Matrix metalloproteinase, Neuromuscular junction, Podosome

Cell BiologyNeuroscience

Biology and Medicine (M)

17100718

General Research Fund (GRF)

2018

Completed

1 To examine the spatiotemporal assembly of PLSs by ECM micropatterns for the formation of aneural AChR clusters. In order to understand how ECM proteins regulate PLS assembly, we will employ the multiphoton biofabrication technique to dissect the role of ECM geometry and stiffness in the spatiotemporal regulation of PLS assembly for the formation of aneural AChR clusters in live cells. 2 To investigate the local degradation of ECM proteins for the remodeling of aneural AChR clusters via PLS-directed surface insertion of MT1-MMP. In order to understand the functions of PLSs in skeletal muscles, we will test an exciting hypothesis that PLS directs the surface targeting of MT1-MMP via microtubule-capturing mechanisms, thus it functions to control the stability and remodeling of aneural AChR clusters by locally modulating ECM environment. 3 To study the regulation of synaptic AChR clustering and remodeling by MT1-MMP surface insertion in vitro and in vivo. As the cellular and molecular mechanisms underlying the regulation of AChR re-distribution in response to synaptic induction remain poorly understood, we will determine if PLS-directed MT1-MMP surface insertion regulates the clustering and remodeling of synaptic AChR clusters at the nascent postsynaptic sites, and the dispersal of aneural AChR clusters in nerve-muscle co-cultures and in MT1-MMP-deficient animals.