Teneurins are a family of phylogenetically conserved single-pass

transmembrane A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...

glycoproteins Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosy ...

expressed during

pattern formation The science of pattern formation deals with the visible, ( statistically) orderly outcomes of self-organization and the common principles behind similar patterns in nature. In developmental biology, pattern formation refers to the generation of ...

and

morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...

. The name refers to "ten-a" (from "

tenascin Tenascins are extracellular matrix glycoproteins. They are abundant in the extracellular matrix of developing vertebrate embryos and they reappear around healing wounds and in the stroma of some tumors. Types There are four members of the tenas ...

-like protein, accessory") and " neurons", the primary site of teneurin expression. Ten-m refers to tenascin-like protein major. Teneurins are highly conserved between ''Drosophila'', ''C. elegans'' and

vertebrates Vertebrates () comprise all animal taxa within the subphylum Vertebrata () (chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with c ...

. 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. 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 In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

. A peptide derived from the terminus of the extracellular domain shares structural homology with certain

neuropeptides Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

. 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 ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...

melanogaster'', the teneurin family is conserved from '' Caenorhabditis elegans'' (''ten-1'') to vertebrates, in which four

paralog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...

s exist (teneurin-1 to -4 or odz-1 to -4). Their distinct

protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of ...

architecture is highly conserved between

invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...

and

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () (chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with c ...

teneurins, particularly in the

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

part. The

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

domains of Ten-a, Ten-m/Odz and ''

C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...

'' 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

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s are remarkably similar.

Function

Teneurins translocate to the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...

where they regulate transcriptional activity. Teneurins promote

neurite A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in cultur ...

outgrowth and cell adhesion. The intracellular domain interacts with the DNA-binding transcriptional repressors and also regulate the activity of

s. Additionally, they have been known to interact with the cytoskeleton adaptor protein, CAP/ponsin, suggesting cell signalling roles and regulation of actin organisation. Teneurin-3 regulates the structural and functional wiring of

retinal ganglion cells A retinal ganglion cell (RGC) is a type of neuron located near the inner surface (the ganglion cell layer) of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina ...

in the vertebrate

visual system The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina containing photoreceptor cells, the optic nerve, the optic tract and the visual cortex) which gives organisms the sense of sight (th ...

Structure

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

C terminal domain

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

N terminal domain

The teneurin intracellular (IC) domain (∼300–400 aa) is located at the N-terminus and contains a number of conserved putative

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...

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

s. 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.