Skip to content

Research at St Andrews

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

Research output: Contribution to journalArticle



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

School/Research organisations


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
Issue number5
Early online date8 Jan 2013
Publication statusPublished - Mar 2013

    Research areas

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

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Reduced plasma magnesium levels in type-1 diabetes associate with prothrombotic changes in fibrin clotting and fibrinolysis

    Sobczak, A. I. S., Phoenix, F. A., Pitt, S. J., Ajjan, R. A. & Stewart, A. J., 11 Nov 2019, (Accepted/In press) In : Thrombosis and Haemostasis.

    Research output: Contribution to journalArticle

  2. A metalloproteomic analysis of interactions between plasma proteins and zinc: elevated fatty acid levels affect zinc distribution

    Coverdale, J. P. C., Barnett, J. P., Adamu, A. H., Griffiths, E. J., Stewart, A. J. & Blindauer, C. A., 1 Nov 2019, In : Metallomics. 11, 11, p. 1805-1819 15 p.

    Research output: Contribution to journalArticle

  3. Plasma non-esterified fatty acids contribute to increased coagulability in type-2 diabetes through altered plasma zinc speciation

    Sobczak, A. I. S., Katundu, K. G. H., Phoenix, F. A., Khazaipoul, S., Yu, R., Lampiao, F., Stefanowicz, F., Blindauer, C. A., Pitt, S. J., Smith, T. K., Ajjan, R. A. & Stewart, A. J., 28 Aug 2019, In : biorxiv. 38 p.

    Research output: Contribution to journalArticle

  4. Changes in plasma free fatty acids associated with type-2 diabetes

    Sobczak, A. I. S., Blindauer, C. A. & Stewart, A. J., 28 Aug 2019, In : Nutrients. 11, 9, 42 p., 2022.

    Research output: Contribution to journalReview article

  5. Sub-micromolar pulse dipolar EPR spectroscopy reveals increasing CuII-labelling of double-histidine motifs with lower temperature

    Wort, J. L., Ackermann, K., Giannoulis, A., Stewart, A. J., Norman, D. G. & Bode, B. E., 19 Aug 2019, In : Angewandte Chemie - International Edition. 58, 34, p. 11681-11685 5 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Synaptic vesicle exocytosis and increased cytosolic calcium are both necessary but not sufficient for activity-dependent bulk endocytosis

    Morton, A., Marland, J. R. K. & Cousin, M. A., Aug 2015, In : Journal of Neurochemistry. 134, 3, p. 405-415 11 p.

    Research output: Contribution to journalArticle

  2. Dietary energy substrates reverse early neuronal hyperactivity in a mouse model of Alzheimer's disease

    Zilberter, M., Ivanov, A., Ziyatdinova, S., Mukhtarov, M., Malkov, A., Alpar, A., Tortoriello, G., Botting, C. H., Fueloep, L., Osypov, A. A., Pitkanen, A., Tanila, H., Harkany, T. & Zilberter, Y., Apr 2013, In : Journal of Neurochemistry. 125, 1, p. 157-171 15 p.

    Research output: Contribution to journalArticle

  3. Palmitoylation of the synaptic vesicle fusion machinery

    Prescott, G. R., Gorleku, O. A., Greaves, J. & Chamberlain, L. H., Aug 2009, In : Journal of Neurochemistry. 110, 4, p. 1135-1149 15 p.

    Research output: Contribution to journalReview article

  4. Collapsin response mediator protein-2 hyperphosphorylation is an early event in Alzheimer’s disease progression.

    Cole, A., Noble, W., van Aalten, L., Yoshida, H., Plattner, F., Meimaridou, R., Hogan, D., La Francois, J., Taylor, M., Gunn-Moore, F. J., Verkhratsky, A., Oddo, S., La Ferla, F., Duff, K., Goedert, M., Giese, K., Dineley, K., Richardson, J., Yan, SD., Hanger, D. & 2 others, Allan, A. & Sutherland, C., Nov 2007, In : Journal of Neurochemistry. 103, p. 1132-1144 13 p.

    Research output: Contribution to journalArticle

ID: 40641417