Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/129131
Title: REGULATION OF ACETYLCHOLINE RECEPTOR ENDOCYTOSIS IN NEUROMUSCULAR DISEASES
Authors: BAO JINGXIAN
Keywords: Aneural, AChR, NMJ, Podosomes, ECM, Integrin
Issue Date: 26-Jul-2016
Source: BAO JINGXIAN (2016-07-26). REGULATION OF ACETYLCHOLINE RECEPTOR ENDOCYTOSIS IN NEUROMUSCULAR DISEASES. ScholarBank@NUS Repository.
Abstract: Postsynaptic enrichment of muscle acetylcholine receptors (AChRs) is crucial for the development of neuromuscular junctions (NMJs). However, pre-patterned AChR clusters can form in pure muscle cultures and undergo a very similar topological transformation as the postsynaptic machinery at NMJ, which challenges the prevalent view that neural factors induce postsynaptic differentiation. To better understand the role of aneural AChR clusters in the maturation of neuromuscular synapses, we co-cultured Xenopus neurons with muscles that lacked aneural AChR clusters. We found that these synapses were incapable to generate stable synaptic AChR clustering. We also made use of photobleaching technique to support the hypothesis that both spontaneously formed diffused and clustered AChRs are recruited to the sites of nerve-muscle contacts. Thus, normal postsynaptic apparatus is required for synapse development and function. Previous studies showed that podosomes, actin-rich adhesive structures, mediate the remodeling process of aneural AChR clusters by degrading the extracellular matrix (ECM). To further investigate molecular mechanisms of postsynaptic maturation, we utilized polydimethylsiloxane (PDMS) micro-contact printing to test the localization of aneural AChR clusters on micro-patterned ECM substrates. We found that aneural AChR clusters are spatially correlated with the micro-patterns of integrin-binding ECM. In addition, we also tested synaptic AChR clustering on these micro-patterned substrates. Most nerve-induced AChR patterns were detected at nerve-muscle contacts formed inside micro-patterns. These results revealed a critical role of ECM in developing topological complexity in postsynaptic cells and forming functional conjunctions in synapses.
URI: http://scholarbank.nus.edu.sg/handle/10635/129131
Appears in Collections:Master's Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Jingxians Master Thesis.pdf7.07 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

77
checked on Feb 24, 2018

Download(s)

31
checked on Feb 24, 2018

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.