M6a acts as a nerve growth factor-gated Ca(2+) channel in neuronal differentiation

Biochem Biophys Res Commun. 2002 Oct 4;297(4):722-8. doi: 10.1016/s0006-291x(02)02284-2.


To elucidate the function of M6a, which is a neuron-specific membrane glycoprotein of the brain and possesses putative phosphorylation sites for protein kinase C (PKC), we established rat M6a cDNA expression vector-transfected PC12 cells. These transfectants exhibited high susceptibilities to nerve growth factor (NGF) for neuronal differentiation. Interestingly, we found that Ca(2+) influx in these transfectants was significantly augmented by the treatment of NGF, but not epidermal growth factor (EGF), which stimulates PC12 cell growth. NGF-dependent augmentation of Ca(2+) influx was detected within 3h and severely inhibited by EGTA- and PKC-specific inhibitors. Anti-M6 antibody suppressed both NGF-triggered Ca(2+) influx and neuronal differentiation. These results support the idea that M6a implicates in neuronal differentiation as a novel Ca(2+) channel gated selectively by phosphorylation with PKC in the downstream of NGF signaling pathway.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Cell Differentiation / physiology*
  • Cerebellum / metabolism
  • Cloning, Molecular
  • DNA Primers
  • Gene Expression Regulation / drug effects
  • Kinetics
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Molecular Sequence Data
  • Nerve Growth Factor / pharmacology*
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology*
  • Open Reading Frames
  • PC12 Cells
  • Pheochromocytoma
  • Rats
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic / drug effects
  • Transfection


  • Calcium Channels
  • DNA Primers
  • Gpm6a protein, rat
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Recombinant Proteins
  • Nerve Growth Factor