Interplay in neural functions of cell adhesion molecule close homolog of L1 (CHL1) and Programmed Cell Death 6 (PDCD6)

Gabriele Loers, Thomas Theis, Helen Baixia Hao, Ralf Kleene, Sanjana Arsha, Nina Samuel, Neha Arsha, Wise Young, Melitta Schachner

Research output: Contribution to journalArticlepeer-review

Abstract

Close homolog of L1 (CHL1) is a cell adhesion molecule of the immunoglobulin superfamily. It promotes neuritogenesis and survival of neurons in vitro. In vivo, CHL1 promotes nervous system development, regeneration after trauma, and synaptic function and plasticity. We identified programmed cell death 6 (PDCD6) as a novel binding partner of the CHL1 intracellular domain (CHL1-ICD). Co-immunoprecipitation, pull-down assay with CHL1-ICD, and proximity ligation in cerebellum and pons of 3-day-old and 6-month-old mice, as well as in cultured cerebellar granule neurons and cortical astrocytes indicate an association between PDCD6 and CHL1. The Ca2+-chelator BAPTA-AM inhibited the association between CHL1 and PDCD6. The treatment of cerebellar granule neurons with a cell-penetrating peptide comprising the cell surface proximal 30 N-terminal amino acids of CHL1-ICD inhibited the association between CHL1 and PDCD6 and PDCD6- and CHL1-triggered neuronal survival. These results suggest that PDCD6 contributes to CHL1 functions in the nervous system.

Original languageEnglish (US)
Pages (from-to)43-59
Number of pages17
JournalFASEB BioAdvances
Volume4
Issue number1
DOIs
StatePublished - Jan 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cancer Research
  • Molecular Medicine
  • Physiology

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