期刊
BIOMEDICINES
卷 10, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines10010102
关键词
neuritogenesis; NOG motif; L1CAM; homophilic binding; biomimetic peptide; CRASH syndrome; neurodevelopmental disorder; regenerative medicine; neuronal differentiation
Homo- and heterophilic binding mediated by the immunoglobulin (Ig)-like repeats of cell adhesion molecules play a crucial role in cell-cell and cell-extracellular matrix interactions. L1CAM is vital for neuronal differentiation in both mature and developing nervous systems, and its functional interactions are mainly mediated by Ig2-Ig2 binding. X-linked mutations in the human L1CAM gene result in L1 diseases, including the commonly diagnosed CRASH neurodevelopmental syndrome. In silico simulations have provided a molecular rationale for CRASH phenotypes caused by specific mutations in the homophilic binding region of Ig2. Synthetic peptides reproducing this region can mimic the neuritogenic capacity of L1CAM and rescue neuritogenesis in a cellular model of the CRASH syndrome, where the full L1CAM ectodomain is ineffective.
Homo- and heterophilic binding mediated by the immunoglobulin (Ig)-like repeats of cell adhesion molecules play a pivotal role in cell-cell and cell-extracellular matrix interactions. L1CAM is crucial to neuronal differentiation, in both mature and developing nervous systems, and several studies suggest that its functional interactions are mainly mediated by Ig2-Ig2 binding. X-linked mutations in the human L1CAM gene are summarized as L1 diseases, including the most diagnosed CRASH neurodevelopmental syndrome. In silico simulations provided a molecular rationale for CRASH phenotypes resulting from mutations I179S and R184Q in the homophilic binding region of Ig2. A synthetic peptide reproducing such region could both mimic the neuritogenic capacity of L1CAM and rescue neuritogenesis in a cellular model of the CRASH syndrome, where the full L1CAM ectodomain proved ineffective. Presented functional evidence opens the route to the use of L1CAM-derived peptides as biotechnological and therapeutic tools.
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