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Regulation of neural circuit formation by protocadherins
Journal article   Open access   Peer reviewed

Regulation of neural circuit formation by protocadherins

Stacey L Peek, Kar Men Mah and Joshua A Weiner
Cellular and molecular life sciences : CMLS, Vol.74(22), pp.4133-4157
11/2017
DOI: 10.1007/s00018-017-2572-3
PMCID: PMC5643215
PMID: 28631008
url
https://doi.org/10.1007/s00018-017-2572-3View
Published (Version of record) Open Access

Abstract

The protocadherins (Pcdhs), which make up the most diverse group within the cadherin superfamily, were first discovered in the early 1990s. Data implicating the Pcdhs, including ~60 proteins encoded by the tandem Pcdha, Pcdhb, and Pcdhg gene clusters and another ~10 non-clustered Pcdhs, in the regulation of neural development have continually accumulated, with a significant expansion of the field over the past decade. Here, we review the many roles played by clustered and non-clustered Pcdhs in multiple steps important for the formation and function of neural circuits, including dendrite arborization, axon outgrowth and targeting, synaptogenesis, and synapse elimination. We further discuss studies implicating mutation or epigenetic dysregulation of Pcdh genes in a variety of human neurodevelopmental and neurological disorders. With recent structural modeling of Pcdh proteins, the prospects for uncovering molecular mechanisms of Pcdh extracellular and intracellular interactions, and their role in normal and disrupted neural circuit formation, are bright.
 Dendrites - metabolism Animals Synapses - metabolism Cadherins - metabolism Signal Transduction Humans Nervous System Diseases - metabolism Axons - physiology Neurons - metabolism Nervous System Diseases - pathology

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