PAR3–PAR6–atypical PKC polarity complex proteins in neuronal polarization

Abstract

Polarity is a fundamental feature of cells. Protein complexes, including the PAR3-PAR6-aPKC complex, have conserved roles in establishing polarity across a number of eukaryotic cell types. In neurons, polarity is evident as distinct axonal versus dendritic domains. The PAR3, PAR6, and aPKC proteins also play important roles in neuronal polarization. During this process, either aPKC kinase activity, the assembly of the PAR3-PAR6-aPKC complex or the localization of these proteins is regulated downstream of a number of signaling pathways. In turn, the PAR3, PAR6, and aPKC proteins control various effector molecules to establish neuronal polarity. Herein, we discuss the many signaling mechanisms and effector functions that have been linked to PAR3, PAR6, and aPKC during the establishment of neuronal polarity.

Axonogenesis Is Coordinated by Neuron-Specific Alternative Splicing Programming and Splicing Regulator PTBP2

“…These genes contain a wide range of functions associated with axonogenesis. For example, Pard3 is a key component of the Par polarity complex (PAR3/PAR6/aPKC) essential to polarity of many cell types including neurons (Hapak et al, 2018). Myo5a and Kif21a are molecular motors responsible for cargo transports.…”

Spatiotemporal regulation of GSK3β levels by miRNA-26a controls axon development in cortical neurons

“…The morphological polarisation of pyramidal neurons through the development of multiple dendrites and a long axonal projection is one of the most complex structural and functional challenges faced by any cell type. The mechanisms, both cellular and molecular, that control this process have been extensively investigated, leading to the identification of many important intracellular signalling pathways and molecules, including phosphoinositide 3-kinase (PI3K), Ras homologous (Rho)-GTPase, Par3/6, mammalian target of rapamycin (mTOR) and protein kinase A (PKA) (Arimura and Kaibuchi, 2007;Barnes and Polleux, 2009;Hapak et al, 2018). Among these, glycogen synthase kinase 3β (GSK3β) has been positioned at a signalling crossroads where it coordinates the complex emergence of axon/dendrite morphology in neurons (Kim and Snider, 2011).…”

Nup358 regulates microridge length by controlling SUMOylation-dependent activity of aPKC in zebrafish epidermis

“…The kinase component of Par polarity complex, aPKC, phosphorylates multiple substrates such as Lgl, Numb and Par1 (Hapak et al, 2018) to achieve spatio-temporal regulation of processes that are involved in the establishment and maintenance of cell polarity. This requires a tight regulation of aPKC activity.…”