CJCADR Forum Seminar at QBI: Implication of phospholipase D1 generated phosphatidic acid in neurosecretion and neuronal development
Event Details
- Date:
- Thursday, 13 August 2015 - Thursday, 13 August 2015
- Time:
- 9:00 am - 10:00 am
- Room:
- QBI Level 7 Auditorium
- UQ Location:
- Queensland Brain Institute (St Lucia)
- URL:
- http://www.qbi.uq.edu.au/neuroscience-seminars
- Event category(s):
Event Contact
- Name:
- Ms Deirdre Wilson
- Phone:
- 66300
- Email:
- d.wilson5@uq.edu.au
- Org. Unit:
- Queensland Brain Institute
Event Description
- Full Description:
- Dr Nicolas Vitale,
Research Director/Group Leader, Institute of Cellular and Integrative Neurosciences, University of Strasbourg, Strasbourg, France
Title: Implication of phospholipase D1 generated phosphatidic acid in neurosecretion and neuronal development
Abstract:
Exocytosis of neurotransmitters and hormones occurs through the fusion of secretory vesicles with the plasma membrane. This highly regulated process involves key proteins such as SNAREs but also specific lipids at sites of membrane fusion. Phospholipases D (PLD1/2) have recently emerged as promoters of membrane fusion in various exocytotic events potentially by providing fusogenic cone-shaped phosphatidic acid (PA). Overexpression and silencing approaches have suggested that PLD1 plays a positive role in secretory granule exocytosis. Using novel pharmacological and genetic approaches we now strengthen this model. Amperometric recordings from mice PLD1-/- chromaffin cells in culture suggest that PA favors a late step in membrane fusion. Using a molecular probe for PA, I will also show that the fusogenic lipid accumulates at the plasma membrane facing chromaffin granules that appeared morphologically docked at the electronic microscopy level, a process that is regulated by the ribosomal S6 kinase 2 (RSK2). I will also show that neurons cultured from mice deficient for Rsk2, a model for the Coffin-Lowry syndrome (CLS), a syndromic form of mental retardation with growth defect, exhibit a significant delay in development in a pattern very similar to that shown by neurons cultured from Pld1 knockout mice. We found that gene silencing of Pld1 or Rsk2, as well as acute pharmacological inhibition of PLD1 or RSK2 strongly impaired neuronal growth factor (NGF)-induced neurite outgrowth from PC12 cells. NGF triggered RSK2-dependent phosphorylation of PLD1 leading to the synthesis of phosphatidic acid at the site of neurite growth. NGF-induced neurite outgrowth was severely inhibited in PC12 cells silenced for RSK2 expression, but expression of a phosphomimetic PLD1 mutant was able to rescue the growth defect, revealing that PLD1 is the major target of RSK2 in neurite formation. Finally PLD1 and RSK2 inhibitors altered NGF-induced VAMP-7 vesicle exocytosis. These findings suggest that the loss of function mutations in RSK2 that lead to CLS and neuronal deficits are related to defects in hormonal release and neuronal growth due to impaired RSK2-dependent PLD1 activity.
Directions to UQ
- Google Map:
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- Directions:
- St Lucia Campus | Gatton campus.
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