TY - JOUR
T1 - MMP-mediated modulation of ECM environment during axonal growth and NMJ development
AU - Chan, Zora Chui-Kuen
AU - Oentaryo, Marilyn Janice
AU - Lee, Chi Wai
N1 - This work was partly supported by the Early Career Grant 27102316 and General Research Fund 17100718 and 17100219 from Research Grants Council of Hong Kong, the Health and Medical Research Fund 04151086 from Food and Health Bureau of Hong Kong, Liu Po Shan/Dr Vincent Liu Endowment Fund for Motor Neurone Disease 203900134 from The University of Hong Kong to CWL.
PY - 2020/4
Y1 - 2020/4
N2 - Motor neurons, skeletal muscles, and perisynaptic Schwann cells interact with extracellular matrix (ECM) to form the tetrapartite synapse in the peripheral nervous system. Dynamic remodeling of ECM composition is essential to diversify its functions for distinct cellular processes during neuromuscular junction (NMJ) development. In this review, we give an overview of the proteolytic regulation of ECM proteins, particularly by secreted and membrane-type matrix metalloproteinases (MMPs), in axonal growth and NMJ development. It is suggested that MMP-2, MMP-9, and membrane type 1-MMP (MT1-MMP) promote axonal outgrowth and regeneration upon injury by clearing the glial scars at the lesion site. In addition, these MMPs also play roles in neuromuscular synaptogenesis, ranging from spontaneous formation of synaptic specializations to activity-dependent synaptic elimination, via proteolytic cleavage or degradation of growth factors, neurotrophic factors, and ECM molecules. For instance, secreted MMP-3 has been known to cleave agrin, the main postsynaptic differentiation inducer, further highlighting the importance of MMPs in NMJ formation and maintenance. Furthermore, the increased level of several MMPs in myasthenia gravis (MG) patient suggest the pathophysiological mechanisms of MMP-mediated proteolytic degradation in MG pathogenesis. Finally, we speculate on potential major future directions for studying the regulatory functions of MMP-mediated ECM remodeling in axonal growth and NMJ development.
AB - Motor neurons, skeletal muscles, and perisynaptic Schwann cells interact with extracellular matrix (ECM) to form the tetrapartite synapse in the peripheral nervous system. Dynamic remodeling of ECM composition is essential to diversify its functions for distinct cellular processes during neuromuscular junction (NMJ) development. In this review, we give an overview of the proteolytic regulation of ECM proteins, particularly by secreted and membrane-type matrix metalloproteinases (MMPs), in axonal growth and NMJ development. It is suggested that MMP-2, MMP-9, and membrane type 1-MMP (MT1-MMP) promote axonal outgrowth and regeneration upon injury by clearing the glial scars at the lesion site. In addition, these MMPs also play roles in neuromuscular synaptogenesis, ranging from spontaneous formation of synaptic specializations to activity-dependent synaptic elimination, via proteolytic cleavage or degradation of growth factors, neurotrophic factors, and ECM molecules. For instance, secreted MMP-3 has been known to cleave agrin, the main postsynaptic differentiation inducer, further highlighting the importance of MMPs in NMJ formation and maintenance. Furthermore, the increased level of several MMPs in myasthenia gravis (MG) patient suggest the pathophysiological mechanisms of MMP-mediated proteolytic degradation in MG pathogenesis. Finally, we speculate on potential major future directions for studying the regulatory functions of MMP-mediated ECM remodeling in axonal growth and NMJ development.
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85080973880&origin=inward
U2 - 10.1016/j.neulet.2020.134822
DO - 10.1016/j.neulet.2020.134822
M3 - Journal article
SN - 0304-3940
VL - 724
JO - Neuroscience Letters
JF - Neuroscience Letters
M1 - 134822
ER -