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

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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.

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Abbreviations

AIS:

Axon-initial segment

AMPK:

AMP-activated protein kinase

aPKC:

Atypical protein kinase C

BDNF:

Brain-derived neurotrophic factor

CaSR:

Extracellular calcium-sensing receptor

CRIB:

CDC42/RAC interactive binding

CRMP-2:

Collapsin response mediator protein-2

DRG:

Dorsal root ganglia

DSC:

Dorsal spinal commissure

Ig:

Immunoglobulin

IZ:

Intermediate zone

JIP-1:

c-Jun N-terminal kinase interacting protein-1

KLC:

Kinesin light chain

MAPK:

Mitogen-activated protein kinase

mEPSC:

Miniature excitatory postsynaptic current

MTOC:

Microtubule organizing center

MTs:

Microtubules

Myr:

Myristoylated

NGF:

Nerve growth factor

NGL-2:

Netrin-G-ligand-2

PB1:

Phox/Bem1

PDZ:

PSD95-DLG1-ZO1

PH:

Pleckstrin homology

PI3-K:

Phosphoinositide 3-kinase

PNS:

Peripheral nervous system

PtdIns:

Phosphatidylinositol

RAL:

Ras-like

RGC:

Retinal ganglion cells

Rheb:

Ras homolog enriched in brain

SCG:

Superior cervical ganglion

SIRT-2:

Sir-two-homolog-2

SVZ:

Subventricular zone

TJ:

Tight junction

TrkA:

Tropomyosin-related kinase A

WT:

Wild type

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Acknowledgements

The authors would like to thank Edward K. Mandel for the discussions. CVR is a HHMI Faculty Scholar (Grant 55108561).

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Authors and Affiliations

  1. Department of Medicine, School of Medicine, University of Minnesota, 401 East River Parkway, Minneapolis, MN, 55455, USA

    Sophie M. Hapak

  2. Department of Immunobiology, School of Medicine, Yale University, 300 Cedar Street, New Haven, CT, 06520, USA

    Carla V. Rothlin

  3. Department of Neurology, School of Medicine, Yale University, 300 George Street, New Haven, CT, 06511, USA

    Sourav Ghosh

  4. Department of Pharmacology, School of Medicine, Yale University, 333 Cedar Street, New Haven, CT, 06520, USA

    Carla V. Rothlin & Sourav Ghosh

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  1. Sophie M. Hapak
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Correspondence to Sophie M. Hapak.

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Hapak, S.M., Rothlin, C.V. & Ghosh, S. PAR3–PAR6–atypical PKC polarity complex proteins in neuronal polarization. Cell. Mol. Life Sci. 75, 2735–2761 (2018). https://doi.org/10.1007/s00018-018-2828-6

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  • DOI: https://doi.org/10.1007/s00018-018-2828-6

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