Phospholipase C-η2 is required for retinoic acid-stimulated neurite growth

J Neurochem. 2013 Mar;124(5):632-44. doi: 10.1111/jnc.12122. Epub 2013 Jan 8.


Phospholipase C-η2 is a recently identified phospholipase C (PLC) implicated in the regulation of neuronal differentiation/maturation. PLCη2 activity is triggered by intracellular calcium mobilization and likely serves to amplify Ca²⁺ signals by stimulating further Ca²⁺ release from Ins(1,4,5)P₃-sensitive stores. The role of PLCη2 in neuritogenesis was assessed during retinoic acid (RA)-induced Neuro2A cell differentiation. PLCη2 expression increased two-fold during a 4-day differentiation period. Stable expression of PLCη2-targetted shRNA led to a decrease in the number of differentiated cells and total length of neurites following RA-treatment. Furthermore, RA response element activation was perturbed by PLCη2 knockdown. Using a bacterial two-hybrid screen, we identified LIM domain kinase 1 (LIMK1) as a putative interaction partner of PLCη2. Immunostaining of PLCη2 revealed significant co-localization with LIMK1 in the nucleus and growing neurites in Neuro2A cells. RA-induced phosphorylation of LIMK1 and cAMP-responsive element-binding protein was reduced in PLCη2 knock-down cells. The phosphoinositide-binding properties of the PLCη2 PH domain, assessed using a FRET-based assay, revealed this domain to possess a high affinity toward PtdIns(3,4,5)P₃. Immunostaining of PLCη2 together with PtdIns(3,4,5)P₃ in the Neuro2A cells revealed a high degree of co-localization, indicating that PtdIns(3,4,5)P₃ levels in cellular compartments are likely to be important for the spatial control of PLCη2 signaling.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Lim Kinases / metabolism
  • Mice
  • Neurites / drug effects
  • Neurites / metabolism*
  • Neurons / cytology*
  • Neurons / metabolism*
  • Phosphoinositide Phospholipase C / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tretinoin / pharmacology*


  • Tretinoin
  • Lim Kinases
  • Limk1 protein, mouse
  • Phosphoinositide Phospholipase C