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Functional Diversity of Neuronal Cell Adhesion and Recognition Molecule L1CAM through Proteolytic Cleavage

期刊

CELLS
卷 11, 期 19, 页码 -

出版社

MDPI
DOI: 10.3390/cells11193085

关键词

cell adhesion and recognition; proteolysis; L1; NCAM; ectodomain shedding

资金

  1. Bulgarian Ministry of Education and Science [DN 13/10]
  2. Ruhr University Bochum, Germany [F957N-2019]
  3. German Academic Exchange Service (DAAD) [57560786]
  4. National Program European Research Networks of the Bulgarian Ministry of Education (project TransBrain)

向作者/读者索取更多资源

The neuronal cell adhesion and recognition molecule L1 not only maintains cell adhesion through interactions, but also enhances cell motility when cleaved into fragments. These fragments can be released into the extracellular space or internalized into the nucleus, transmitting extracellular signals to the cell interior. Proteolysis of L1 contributes to its functional diversity and plays a vital role in morphogenic events and regenerative processes in neuronal cells. Stimulating L1 proteolysis shows promise as a therapeutic tool for injured nervous systems. The collective findings shed light on the diverse functions of L1 and its fragments, and provide mechanistic insights into adhesion molecule proteolysis in the developing and diseased nervous system.
The neuronal cell adhesion and recognition molecule L1 does not only 'keep cells together' by way of homophilic and heterophilic interactions, but can also promote cell motility when cleaved into fragments by several proteases. It has largely been thought that such fragments are signs of degradation. Now, it is clear that proteolysis contributes to the pronounced functional diversity of L1, which we have reviewed in this work. L1 fragments generated at the plasma membrane are released into the extracellular space, whereas other membrane-bound fragments are internalised and enter the nucleus, thus conveying extracellular signals to the cell interior. Post-translational modifications on L1 determine the sequence of cleavage by proteases and the subcellular localisation of the generated fragments. Inside the neuronal cells, L1 fragments interact with various binding partners to facilitate morphogenic events, as well as regenerative processes. The stimulation of L1 proteolysis via injection of L1 peptides or proteases active on L1 or L1 mimetics is a promising tool for therapy of injured nervous systems. The collective findings gathered over the years not only shed light on the great functional diversity of L1 and its fragments, but also provide novel mechanistic insights into the adhesion molecule proteolysis that is active in the developing and diseased nervous system.

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