aPKC in neuronal differentiation, maturation and function

Abstract

The atypical Protein Kinase Cs (aPKCs)—PRKCI, PRKCZ and PKMζ—form a subfamily within the Protein Kinase C (PKC) family. These kinases are expressed in the nervous system, including during its development and in adulthood. One of the aPKCs, PKMζ, appears to be restricted to the nervous system. aPKCs are known to play a role in a variety of cellular responses such as proliferation, differentiation, polarity, migration, survival and key metabolic functions such as glucose uptake, that are critical for nervous system development and function. Therefore, these kinases have garnered a lot of interest in terms of their functional role in the nervous system. Here we review the expression and function of aPKCs in neural development and in neuronal maturation and function. Despite seemingly paradoxical findings with genetic deletion versus gene silencing approaches, we posit that aPKCs are likely candidates for regulating many important neurodevelopmental and neuronal functions, and may be associated with a number of human neuropsychiatric diseases.

A Monolayer System for the Efficient Generation of Motor Neuron Progenitors and Functional Motor Neurons from Human Pluripotent Stem Cells

“…In these conditions, hiPSCs were consistently differentiated into neuroepithelial cells in 6 days ( Figure 1 B). At DIV6, the cultures were characterized by the absence of residual hiPSCs as shown by the lack of OCT4 +ve and NANOG +ve cells, and by the presence of neural cells arranged in neural rosette structures and exhibiting marked immunoreactivity for NESTIN and for the neural rosette markers ZO1 and aPKC ( Figure 1 B) [ 29 , 30 ].…”

Domestication modulates the expression of genes involved in neurogenesis in high‐quality eggs of Sander lucioperca

“…However, even these genes were reported to be involved in the development and functioning of the nervous system. This includes neuronal programmed cell death ( casp3 ; Roth & D'Sa, 2001), suppression of apoptosis of neurons ( nckap1l ; Zhong et al, 2019), development of the neurons ( prkcz ; Hapak, Rothlin, & Ghosh, 2019), formation and maintenance of synapses ( dag1 ; Nickolls & Bönnemann, 2018) as well as modulation of the expression of neuron‐associated Tau proteins ( mapt ; Caillet‐Boudin, Buée, Sergeant, & Lefebvre, 2015). All these results indicate that domestication highly affects the nervous system development in finfishes, and the changes are evident in pikeperch even after a single generation in captivity.…”

The potential of mechanistic information organised within the AOP framework to increase regulatory uptake of the developmental neurotoxicity (DNT) in vitro battery of assays

“… [ 78 ] Reelin, ApoER2 and VLDLR [ 81 ] BDNF⁄TrkB interaction, PI3-K, MAP-K [ 82 ] Cdk5, Dab1, Rac1, FAK, Ras, Src, and PI3K [ 83 ] Calm1, Gria1 (GluA1) and Camk4 (calmodulin-signaling network), Hdac2 and Hsbp1 (Akt1-DNA transcription network), Vav3 and Ppm1a [ 84 ] Differentiation and maturation of Neural Stem Cells into distinct neuronal cell types Yes mTORC1/C2, prostaglandin, Histone acetylation/deacetylation, miRNA-9, miRNA-17-92 cluster, miRNA-124, Notch signalling, Wnt, BDNF, retinoic acid signaling. [ 64 , 67 ] SHH and Notch pathway activation (for the maintenance of neural rosette cells) [ 85 ] Wnt/β-catenin pathway, β -catenin/TCF, neurogenin 1 [ 86 ] aPKC, PRKCI and PRKCZ [ 87 ] Wnt factors signal through canonical, β-catenin pathway, planar cell polarity pathway and calcium pathway [ 88 ] Neuron maturation relevant functional modules in protein-protein interaction (PPI) network [ 89 ] Synaptogenesis Yes NMDA-receptor activation, BDNF-Trk signalling, calcium signalling, inositol metabolism, Phospholipase D activity with generation of phosphatidic acid; BDNF-ERK-CREB/decreased activity/phosphorylation [ 65 ] ProSAP1/Shank2, MaGuK family, including SAP90/PSD-95, Munc13, RIMs, ERC/CAST, Piccolo/Aczonin, and Bassoon, Shank1, Neuroligin, and GKAP [ 90 ] Wnt signalling through β-catenin-dependent pathways [ …”