Teneurin

Teneurins are a family of phylogenetically conserved single-pass transmembrane glycoproteins expressed during pattern formation and morphogenesis.[1] The name refers to "ten-a" (from "tenascin-like protein, accessory") and "neurons", the primary site of teneurin expression. Ten-m refers to tenascin-like protein major.

Teneurin
Identifiers
Symbol	Teneurin
Pfam	PF06484
InterPro	IPR009471
Membranome	1168
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Teneurins are highly conserved between Drosophila, C. elegans and vertebrates. In each species, they are expressed by a subset of neurons as well as at sites of pattern formation and morphogenesis. In Drosophila, a teneurin known as ten-m or Odz is a pair-rule gene, and its expression is required for normal development. The knockdown of teneurin (ten-1) expression in C. elegans with RNAi leads to abnormal neuronal pathfinding and abnormal development of the gonads.[2]

The intracellular domain of some, if not all, teneurins can be cleaved and transported to the cell nucleus, where it proposed to act as a transcription factor. A peptide derived from the terminus of the extracellular domain shares structural homology with certain neuropeptides.

There are four teneurin genes in vertebrates, named teneurin-1 through -4. Other names found in the literature include Odz-1 through -4 and Tenm-1 through -4.

History

Originally discovered as ten-m and ten-a in Drosophila melanogaster, the teneurin family is conserved from Caenorhabditis elegans (ten-1) to vertebrates, in which four paralogs exist (teneurin-1 to -4 or odz-1 to -4). Their distinct protein domain architecture is highly conserved between invertebrate and vertebrate teneurins, particularly in the extracellular part. The intracellular domains of Ten-a, Ten-m/Odz and C. elegans TEN-1 are significantly different, both in size and structure, from the comparable domains of vertebrate teneurins, but the extracellular domains of all of these proteins are remarkably similar.

Function

Teneurins translocate to the nucleus where they regulate transcriptional activity. Teneurins promote neurite outgrowth and cell adhesion. The intracellular domain interacts with the DNA-binding transcriptional repressors and also regulate the activity of transcription factors.

Additionally, they have been known to interact with the cytoskeleton adaptor protein, CAP/ponsin, suggesting cell signalling roles and regulation of actin organisation.[3]

Teneurin-3 regulates the structural and functional wiring of retinal ganglion cells in the vertebrate visual system.[4]

Structure

Ten-m1–4, exist as homodimers and undergo homophilic interactions in vertebrates.

C terminal domain

The large C-terminal extracellular domain consists of eight EGF-like repeats (see PROSITEDOC), a region of conserved cysteines and unique YD-repeats.

N terminal domain

Teneurin Intracellular Region
Identifiers
Symbol	Ten_N
Pfam	PF06484
InterPro	IPR009471
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

The teneurin intracellular (IC) domain (∼300–400 aa) is located at the N-terminus and contains a number of conserved putative tyrosine phosphorylation sites, two EF-hand-like calcium-binding motifs, and two polyproline domains. These proline-rich stretches are characteristic of SH3-binding sites. There is considerable divergence between intracellular domains of invertebrate and vertebrate teneurins as well as between different invertebrate proteins.[5][6][7][8][9]

This domain is found in the intracellular N-terminal region of the teneurin family.

Human genes

Human genes encoded teneurin domain proteins (TENM1-4) are list in the infoboxes.

References

1. Tucker RP, Chiquet-Ehrismann R, Chevron MP, Martin D, Hall RJ, Rubin BP (January 2001). "Teneurin-2 is expressed in tissues that regulate limb and somite pattern formation and is induced in vitro and in situ by FGF8". Dev. Dyn. 220 (1): 27–39. doi:10.1002/1097-0177(2000)9999:9999<::AID-DVDY1084>3.0.CO;2-B. PMID 11146505.
2. Drabikowski, Krzysztof; Trzebiatowska, Agnieszka; Chiquet-Ehrismann, Ruth (2005-06-01). "ten-1, an essential gene for germ cell development, epidermal morphogenesis, gonad migration, and neuronal pathfinding in Caenorhabditis elegans". Developmental Biology. 282 (1): 27–38. doi:10.1016/j.ydbio.2005.02.017. ISSN 0012-1606. PMID 15936327.
3. Young TR, Leamey CA (2009). "Teneurins: important regulators of neural circuitry". Int J Biochem Cell Biol. 41 (5): 990–3. doi:10.1016/j.biocel.2008.06.014. PMID 18723111.
4. Antinucci P, Nikolaou N, Meyer MP, Hindges R (2013). "Teneurin-3 specifies morphological and functional connectivity of retinal ganglion cells in the vertebrate visual system". Cell Rep. 5 (3): 582–92. doi:10.1016/j.celrep.2013.09.045. PMC 3898612. PMID 24183672.
5. Minet AD, Rubin BP, Tucker RP, Baumgartner S, Chiquet-Ehrismann R (June 1999). "Teneurin-1, a vertebrate homologue of the Drosophila pair-rule gene ten-m, is a neuronal protein with a novel type of heparin-binding domain". J. Cell Sci. 112 (12): 2019–32. PMID 10341219.
6. Bagutti C, Forro G, Ferralli J, Rubin B, Chiquet-Ehrismann R (July 2003). "The intracellular domain of teneurin-2 has a nuclear function and represses zic-1-mediated transcription". J. Cell Sci. 116 (Pt 14): 2957–66. doi:10.1242/jcs.00603. PMID 12783990.
7. Tucker RP, Chiquet-Ehrismann R (February 2006). "Teneurins: a conserved family of transmembrane proteins involved in intercellular signaling during development". Dev. Biol. 290 (2): 237–45. doi:10.1016/j.ydbio.2005.11.038. PMID 16406038.
8. Tucker RP, Kenzelmann D, Trzebiatowska A, Chiquet-Ehrismann R (2007). "Teneurins: transmembrane proteins with fundamental roles in development". Int. J. Biochem. Cell Biol. 39 (2): 292–7. doi:10.1016/j.biocel.2006.09.012. PMID 17095284.
9. Kenzelmann D, Chiquet-Ehrismann R, Tucker RP (June 2007). "Teneurins, a transmembrane protein family involved in cell communication during neuronal development" (PDF). Cell. Mol. Life Sci. 64 (12): 1452–6. doi:10.1007/s00018-007-7108-9. PMID 17502993.

Further reading

• Baumgartner S, Martin D, Hagios C, Chiquet-Ehrismann R (August 1994). "Tenm, a Drosophila gene related to tenascin, is a new pair-rule gene". EMBO J. 13 (16): 3728–40. doi:10.1002/j.1460-2075.1994.tb06682.x. PMC 395283. PMID 8070401.
• Levine A, Bashan-Ahrend A, Budai-Hadrian O, Gartenberg D, Menasherow S, Wides R (May 1994). "Odd Oz: a novel Drosophila pair rule gene". Cell. 77 (4): 587–98. doi:10.1016/0092-8674(94)90220-8. PMID 7514504.
• Tucker RP, Chiquet-Ehrismann R (February 2006). "Teneurins: a conserved family of transmembrane proteins involved in intercellular signaling during development". Dev. Biol. 290 (2): 237–45. doi:10.1016/j.ydbio.2005.11.038. PMID 16406038.