BM88/Cend1 regulates stimuli-induced intracellular calcium mobilization

Neuropharmacology. 2009 Mar;56(3):598-609. doi: 10.1016/j.neuropharm.2008.10.015. Epub 2008 Nov 13.


In neurogenesis, little is known about signal transduction pathways upstream of gene expression however, mounting evidence suggests that calcium release from internal stores plays a critical role. We have previously demonstrated that BM88 is a neuronal lineage-specific regulator of cell cycle exit and differentiation; we now report a link between BM88 and calcium signaling. Calcium imaging experiments revealed that P2Y-induced calcium mobilization is diminished in mouse neuroblastoma Neuro 2a cells stably transfected with BM88 (N2A-BM88 cells) as compared with N2A cells or N2A cells differentiated with retinoic acid. This effect is not restricted to N2A cells but is also observed in HeLa cells that are transiently transfected with BM88, indicating that cells of both neural and non-neural origin respond similarly. Further, activation of P2Y1 but not purinergic P2X receptors induces proliferation of N2A and to a lesser extent of N2A-BM88 cells. Conversely, knockdown of BM88 facilitates N2A cell proliferation both under stimulating and non-stimulating conditions. Importantly, N2A-BM88 cells are less susceptible to apoptosis triggered by C2-ceramide and exhibit reduced C2-ceramide-induced intracellular calcium release. Higher calcium uptake from mitochondria and/or lower calcium levels inside the endoplasmic reticulum may explain the reduced calcium mobilization in response to BM88. Overall, our data reveal a novel signaling mechanism by which BM88 interferes with calcium release from inositol 1,4,5-trisphosphate-sensitive stores and exerts anti-proliferative and anti-apoptotic functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Amino Acid Sequence
  • Animals
  • Apoptosis / drug effects
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Cell Differentiation
  • Cell Proliferation
  • Intracellular Fluid / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology
  • Neurogenesis
  • Neurons / physiology*
  • Receptors, Purinergic P2 / physiology
  • Sequence Alignment
  • Sphingosine / analogs & derivatives
  • Sphingosine / pharmacology
  • Transfection
  • Tumor Cells, Cultured


  • Cend1 protein, mouse
  • Membrane Proteins
  • N-acetylsphingosine
  • Nerve Tissue Proteins
  • Receptors, Purinergic P2
  • Adenosine Triphosphate
  • Sphingosine
  • Calcium