Neurexin-1-alpha is a
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, respo ...
that in humans is encoded by the ''NRXN1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Neurexin
Neurexins (NRXN) are a family of presynaptic cell adhesion proteins that have roles in connecting neurons at the synapse. They are located mostly on the presynaptic membrane and contain a single transmembrane domain. The extracellular domain ...
s are a family of proteins that function in the vertebrate nervous system as cell adhesion molecules and receptors. They are encoded by several unlinked genes of which two, NRXN1 and
NRXN3
Neurexin-3-alpha is a protein that in humans is encoded by the ''NRXN3'' gene.
Neurexins are a family of proteins that function in the vertebrate nervous system as cell adhesion molecules and receptors. They are encoded by several unlinked genes o ...
, are among the largest known human genes.
Three of the genes (NRXN1-3) utilize two alternate promoters and include numerous alternatively spliced exons to generate thousands of distinct mRNA transcripts and protein isoforms. The majority of transcripts are produced from the upstream promoter and encode alpha-neurexin isoforms; a much smaller number of transcripts are produced from the downstream promoter and encode beta-neurexin isoforms. The alpha-neurexins contain epidermal growth factor-like (EGF-like) sequences and laminin G domains, and have been shown to interact with
neurexophilins. The beta-neurexins lack EGF-like sequences and contain fewer laminin G domains than alpha-neurexins.
Function
Neurexin
Neurexins (NRXN) are a family of presynaptic cell adhesion proteins that have roles in connecting neurons at the synapse. They are located mostly on the presynaptic membrane and contain a single transmembrane domain. The extracellular domain ...
s are
presynaptic membrane
Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous sys ...
cell-adhesion molecule
Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
s that bind primarily to
neuroligin
Neuroligin (NLGN), a type I membrane protein, is a cell adhesion protein on the postsynaptic membrane that mediates the formation and maintenance of synapses between neurons. Neuroligins act as ligands for β-neurexins, which are cell ad ...
s, proteins that have been associated with
autism
The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
. Autism is characterized by a wide range of social and cognitive deficits, which are partially attributed to faulty synaptic communication between
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s.
This lack of communication is oftentimes tied to mutations in NRXN1. Structural variants of NRXN1a (neurexin1 alpha) are consistent with mutations predisposing autism. These alpha neurexins are involved in communication through coupling mechanisms of calcium channels and vesicle exocytosis, to ensure that neurotransmitters are properly released. They are specifically required for glutamate and GABA release.
Implications of neurexin involvement in autism have been determined through deletion in coding exons of NRXN1a, particularly in knockout mice models. These mice showed impaired social functioning, decreased motor response in new situations, and increased aggressive behavior in males.
Social functioning
A social skill is any social competence, competence facilitating Interpersonal relationship, interaction and Social Communication, communication with others where social rules and Interpersonal relationship, relations are created, Human communicat ...
was of major relevance for this gene and its association with
autism spectrum disorder
The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental disorder, neurodevelopmental condition (or conditions) ...
.
Genomics
The gene is found in a single copy on the short arm of chromosome 2 (2p16.3). The gene is 1,112,187 bases in length, is located on the Crick (minus) strand and encodes a protein of 1,477 amino acids (molecular weight 161.883 kDa).
Mutations of this gene that interrupt its expression have been associated with
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
,
autism
The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
, and intellectual disability
NRXN1 mutations and brain disorders.
Interactions
NRXN1 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
NLGN1
Neuroligin-1 is a protein that in humans is encoded by the ''NLGN1'' gene.
This gene encodes a member of the neuroligin family of neuronal cell surface proteins. Neuroligin-1 acts as splice site-specific ligand for β-neurexins and has been shown ...
.
References
Further reading
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External links
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