Biochemical and functional characterisation of αPIX, a specific regulator of axonal and dendritic branching in hippocampal neurons.

Biology of the Cell
Antonio TotaroIvan de Curtis

Abstract

PIX proteins are exchange factors for Rac and Cdc42 GTPases that are differentially expressed in the brain, where they are implicated in neuronal morphogenesis. The PIX family includes the two members αPIX and βPIX, and the gene of αPIX is mutated in patients with intellectual disability. We have analysed the expression of PIX proteins in the developing brain and addressed their role during early hippocampal neuron development. Mass spectrometry identified several βPIX isoforms and a major p75 αPIX isoform in brain and hippocampal cultures. PIX proteins expression increased with time during neuronal differentiation in vitro. The PIX partners GIT1 and GIT2 are also found in brain and their expression was increased during neuronal differentiation. We found that αPIX, but not βPIX, was required for proper hippocampal neuron differentiation, since silencing of αPIX specifically hampered dendritogenesis and axonal branching. Interestingly, the depletion of GIT2 but not GIT1 mimicked the phenotype observed after αPIX knock-down. Over-expression of αPIX specifically enhanced dendritic branching, while both αPIX and βPIX over-expression affected axonal morphology. Again, only over-expression of GIT2, but not GIT1, affected neuritic mor...Continue Reading

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Citations

Apr 30, 2016·Neural Regeneration Research·Yi-Sheng LiWei-Qiang Gao
Jun 18, 2014·Small GTPases·Mirela Spillane, Gianluca Gallo
Mar 29, 2016·Journal of Cellular Physiology·Nicholas RooneyCharles H Streuli
Mar 20, 2018·PloS One·Amanda C MartynRichard T Premont
Jun 13, 2018·Scientific Reports·Alejandro López TobónAndreas W Püschel
Jan 24, 2019·International Journal of Molecular Sciences·Christine E TannaPei-Wen Chen
Jan 10, 2017·Frontiers in Cellular Neuroscience·Sira A FranchiIvan de Curtis

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