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

Petra Popovics, Alexander Gray, Mohammed Arastoo, Deana K. Finelli, Audrey J.L. Tan, Alan J. Stewart*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)632-644
Number of pages13
JournalJournal of Neurochemistry
Issue number5
Early online date12 Dec 2012
Publication statusPublished - Mar 2013
Externally publishedYes

Bibliographical note

© 2012 International Society for Neurochemistry.


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


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