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

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

PLCη2 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 2-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 (RARE) 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 CREB was reduced in PLCη2 knockdown cells. The phosphoinositide-binding properties of the PLCη2 PH domain, assessed using a FRET-based assay, reveal 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
Volume124
Issue number5
Early online date8 Jan 2013
DOIs
Publication statusPublished - Mar 2013

Keywords

  • Cell differentiation
  • Calcium signaling
  • Neurite growth
  • Phospholipase
  • Nuclear receptors
  • Neuroscience

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