Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015;9(3):214-26.
doi: 10.1080/19336918.2014.1000069. Epub 2015 Apr 14.

Protocadherins branch out: Multiple roles in dendrite development

Austin B Keeler  1 , Michael J Molumby, Joshua A Weiner
Affiliations
Review

Protocadherins branch out: Multiple roles in dendrite development

Austin B Keeler et al. Cell Adh Migr. 2015.

Abstract

The proper formation of dendritic arbors is a critical step in neural circuit formation, and as such defects in arborization are associated with a variety of neurodevelopmental disorders. Among the best gene candidates are those encoding cell adhesion molecules, including members of the diverse cadherin superfamily characterized by distinctive, repeated adhesive domains in their extracellular regions. Protocadherins (Pcdhs) make up the largest group within this superfamily, encompassing over 80 genes, including the ∼60 genes of the α-, β-, and γ-Pcdh gene clusters and the non-clustered δ-Pcdh genes. An additional group includes the atypical cadherin genes encoding the giant Fat and Dachsous proteins and the 7-transmembrane cadherins. In this review we highlight the many roles that Pcdhs and atypical cadherins have been demonstrated to play in dendritogenesis, dendrite arborization, and dendritic spine regulation. Together, the published studies we discuss implicate these members of the cadherin superfamily as key regulators of dendrite development and function, and as potential therapeutic targets for future interventions in neurodevelopmental disorders.

Keywords: CNR, Cadherin related neuronal receptor; CTCF, CCCTC-binding factor; CaMKII, Ca2+/calmodulin-dependent protein kinase II.; Celsr, Cadherin EGF LAG 7-pass G-type receptor 1; DSCAM, Down syndrome cell adhesion molecule; Dnmt3b, DNA (cytosine-5-)-methyltransferase 3 β; Ds, Dachsous; EC, extracellular cadherin; EGF, Epidermal growth factor; FAK, Focal adhesion kinase; FMRP, Fragile X mental retardation protein; Fj, Four jointed; Fjx1, Four jointed box 1; GPCR, G-protein-coupled receptor; Gogo, Golden Goal; LIM domain, Lin11, Isl-1 & Mec-3 domain; MARCKS, Myristoylated alanine-rich C-kinase substrate; MEF2, Myocyte enhancer factor 2; MEK3, Mitogen-activated protein kinase kinase 3; PCP, planar cell polarity; PKC, Protein kinase C; PSD, Post-synaptic density; PYK2, Protein tyrosine kinase 2; Pcdh; Pcdh, Protocadherin; RGC, Retinal ganglion cell; RNAi, RNA interference; Rac1, Ras-related C3 botulinum toxin substrate 1; S2 cells, Schneider 2 cells; SAC, starburst amacrine cell; TAF1, Template-activating factor 1; TAO2β, Thousand and one amino acid protein kinase 2 β; TM, transmembrane; arborization; atypical cadherin; branching; cadherin superfamily; cell adhesion; da neuron, dendritic arborization neuron; dendritic; dendritic spine; dendritogenesis; fmi, Flamingo; md neuron, multiple dendrite neuron; neural circuit formation; p38 MAPK, p38 mitogen-activated protein kinase; self avoidance; synaptogenesis.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Clustered and Non-Clustered Protocadherins. Schematic domain structures of the clustered (α-, β-, and γ-) Pcdhs, and of the δ1- and δ2- non-clustered Pcdhs. Domains as indicated by legend; double horizontal line represents the plasma membrane. The domain structure of a classical cadherin is shown for comparison. A summary of known dendritic functions appears above each schematic.
Figure 2.
Figure 2.
Atypical Cadherins. Schematic domain structures of Flamingo, Celsr, and Fat atypical cadherins. Domains as indicated by legend; double horizontal line represents the plasma membrane. A summary of known dendritic functions appears above each schematic. Because Fat proteins have too many cadherin repeats to easily depict in a reasonably-sized figure, the double-diagonal lines indicate continuation of cadherin repeats between the 6th and 29th.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Vaughn JE, Barber RP, Sims TJ. Dendritic development and preferential growth into synaptogenic fields: A quantitative study of Golgi-impregnated spinal motor neurons. Synapse 1988; 2:69-78; PMID:2458630; http://dx.doi.org/10.1002/syn.890020110 - DOI - PubMed
    1. Vaughn J, Anonymous . Fine structure of synaptogenesis in the vertebrate central nervous system. Synapse 1989; 3:255; PMID:2655146; http://dx.doi.org/10.1002/syn.890030312 - DOI - PubMed
    1. Cline H, Haas K. The regulation of dendritic arbor development and plasticity by glutamatergic synaptic input: a review of the synaptotrophic hypothesis. J Physiol 2008; 586:1509; PMID:18202093; http://dx.doi.org/10.1113/jphysiol.2007.150029 - DOI - PMC - PubMed
    1. Jan YN, Jan LY. Branching out: mechanisms of dendritic arborization. Nat Rev Neurosci 2010; 11:316; PMID:20404840; http://dx.doi.org/10.1038/nrn2836 - DOI - PMC - PubMed
    1. Dierssen M, Ramakers GJ. Dendritic pathology in mental retardation: from molecular genetics to neurobiology. Genes, Brain, and Behav 2006; 5 Suppl 2):48; PMID:16681800; http://dx.doi.org/10.1111/j.1601-183X.2006.00224.x - DOI - PubMed

LinkOut - more resources