P1.09. THE ROLE OF CAP2 IN THE NEUROMUSCULAR SYSTEM
Olga Wójcicka1, Teresa De Cicco1, Lara-Jane Kepser2, Jeffery Field3, Marco Rust2, Tomasz J. Prószyński1
1 Synaptogenesis Research Group, Łukasiewicz Research Network PORT – Polish Centre of Technology Development, Stablowicka 147, 54-066, Wrocław, Poland
2 Molecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032 Marburg, Germany
3 Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
INTRODUCTION: The neuromuscular system controls voluntary movement through signals from motoneurons to muscles. This process relies not only on synaptic integrity but also on proper cytoskeletal organization. Actin dynamics and its regulators, such as cyclase-associated protein 2 (Cap2), play a key role in the neuromuscular system . However, the function of Cap2 at the neuromuscular junctions (NMJ) remains unknown.
AIM(S): To understand the role of Cap2 at the neuromuscular system.
METHOD(S): We employed immunohistochemistry, muscles cross-sectioning, and confocal microscopy to investigate NMJ morphology and muscle histology in tissue-specific KO mice.
RESULTS: Muscle-specific Cap2 knockout mice show particularly severe phenotypes, with male mutants exhibiting stunted growth and premature death. Skeletal muscle cross-sections analysis reveals abnormal morphology and actin accumulation, suggesting impaired cytoskeletal organization. These changes appeared in both fast- and slow-twitch muscles, highlighting the essential role of Cap2 in muscle maintenance. At the NMJ, Cap2 loss in systemic KO mice leads to structural abnormalities, such as an increased number of NMJs with atypical sizes, postsynaptic AChR fragmentation, and presynaptic axonal swelling. While motoneuron-specific Cap2 knockouts show presynaptic changes, muscle-specific deletion causes extensive postsynaptic disruption and altered NMJ size, emphasizing the importance of Cap2 in maintaining neuromuscular integrity through its function in the postsynaptic machinery.
CONCLUSIONS: Our findings indicate that Cap2 is essential for the proper function and structural integrity of the neuromuscular system. Its disruption leads to widespread impairments affecting both muscle tissue and neuromuscular synapses. These results highlight the critical role of Cap2 in maintaining overall neuromuscular health and stability.
FINANCIAL SUPPORT: This work has been supported by the Polish National Science Centre, NCN grants 2020/37/N/NZ3/03855; 2022/06/X/NZ4/00774; 2024/52/C/NZ3/00219