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The cell adhesion molecule L1 interacts with nuclear proteins via its intracellular domain
Author(s) -
Girbes Minguez Maria,
WoltersEisfeld Gerrit,
Lutz David,
Buck Friedrich,
Schachner Melitta,
Kleene Ralf
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902242r
Subject(s) - microbiology and biotechnology , nuclear transport , chromatin , biology , nuclear protein , cell nucleus , chemistry , dna , biochemistry , transcription factor , gene , cytoplasm
Proteolytic cleavage of the cell adhesion molecule L1 (L1) in brain tissue and in cultured cerebellar neurons results in the generation and nuclear import of a 30 kDa fragment comprising most of L1's C‐terminal, intracellular domain. In search of molecules that interact with this domain, we performed affinity chromatography with the recombinant intracellular L1 domain and a nuclear extract from mouse brains, and identified potential nuclear L1 binding partners involved in transcriptional regulation, RNA processing and transport, DNA repair, chromatin remodeling, and nucleocytoplasmic transport. By co‐immunoprecipitation and enzyme‐linked immunosorbent assay using recombinant proteins, we verified the direct interaction between L1 and the nuclear binding partners non‐POU domain containing octamer‐binding protein and splicing factor proline/glutamine‐rich. The proximity ligation assay confirmed this close interaction in cultures of cerebellar granule cells. Our findings suggest that L1 fragments regulate multiple nuclear functions in the nervous system. We discuss possible physiological and pathological roles of these interactions in regulation of chromatin structure, gene expression, RNA processing, and DNA repair.