Molecules in focus
Teneurins: Important regulators of neural circuitry

https://doi.org/10.1016/j.biocel.2008.06.014Get rights and content

Abstract

Teneurin (Ten-m/Odz) molecules represent a highly conserved family of four type II transmembrane proteins in vertebrates (Ten-m1–4), which exist as homodimers and undergo homophilic interactions. Each is expressed in distinct, and often interconnected, areas of the developing nervous system. Different Ten-ms have complementary expression patterns. In vitro and in vivo studies support roles for teneurins in promoting neurite outgrowth and cell adhesion. Furthermore, the intracellular domains of at least two teneurins can undergo proteolytic cleavage and translocate to the nucleus where they regulate transcriptional activity. Recent in vivo studies show that teneurins play important roles in regulating connectivity in the nervous system. Knockdown in C. elegans resulted in abnormal axon guidance and cell migration, while targeted deletion of Ten-m3 in mice revealed it is required for the guidance of retinal axons and generation of visual topography. It is likely that all teneurins play important roles during neural development.

Introduction

Vertebrate teneurins (Ten-ms) are a recently discovered family of type II transmembrane glycoproteins, of which gene sequences for four family members have been identified in a number of species including mouse, chicken, and human. The invertebrate homolog for this family of genes was initially discovered in Drosophila by two independent laboratories and was subsequently named Odd Oz (Odz), after the oddless pair-rule phenotype displayed by mutants or tenascin-like protein major (Ten-m), due to the presence of its tenascin-type epidermal growth factor (EGF)-like repeats (see Tucker and Chiquet-Ehrismann, 2006 for review). These molecules have since been found to be conserved across both vertebrate and invertebrate species. Their precise function, however, has not yet been elucidated. In this review, we aim to highlight recent studies which extend previous work and provide direct evidence that teneurins play an important role in specifying connectivity in the developing nervous system.

Section snippets

Structure

To date, most vertebrates examined have been found to possess four teneurin family members (Ten-m1–Ten-m4) which encode large proteins that have a molecular weight ∼300 kDa and are generally composed of ∼2800 aa (see Tucker and Chiquet-Ehrismann, 2006 for detailed review). Teneurins are highly conserved between paralogs and across species (overall amino acid identity ranges from 55–68% between mouse paralogs, and is generally around 90% when vertebrate orthologs are compared), and accordingly

Expression

In all species studied to date, teneurins are most prominently found in the nervous system and are highly regulated during development, however, some family members are additionally expressed in non-neuronal tissues and are closely associated with sites of pattern formation (see Tucker and Chiquet-Ehrismann (2006) for review). In chicken embryo, expression of Ten-m1 and Ten-m2 has been reported in interconnected regions of the nervous system, and furthermore they were largely expressed in

Function

Although the context in which teneurins carry out their role is not fully understood, transfection studies have provided evidence that teneurins can promote neurite outgrowth (Leamey et al., 2008, Rubin et al., 1999) and cell adhesion (Leamey et al., 2008, Rubin et al., 2002) both in vitro and in vivo (for recent reviews see Kenzelmann et al., 2007, Tucker and Chiquet-Ehrismann, 2006).

Recently, a few studies have begun to characterise the role of endogenous teneurins in vivo. Knockdown using

Clinical implications

Genetic, biochemical and expression data all point to important roles for the teneurins in mediating neural development. Consistent with this, the chromosomal locus of Ten-m1 in humans, Xq25, is associated with X-linked mental retardation (reviewed in Tucker and Chiquet-Ehrismann, 2006). Additionally, the binding partner of the IC domain of Ten-m1, MBD1, is associated with autism, whereas mutations of zic1, which interacts with the intracellular domain of Ten-m2 (Bagutti et al., 2003), is

Acknowledgements

The authors thank Kelly Glendining for comments on the manuscript.

References (21)

There are more references available in the full text version of this article.

Cited by (67)

  • Structure, function and therapeutic potential of adhesion GPCRs

    2019, GPCRs: Structure, Function, and Drug Discovery
View all citing articles on Scopus
View full text