LRRTM1 is a brain-expressed imprinted gene that encodes a leucine-rich repeat transmembrane protein that interacts with neurexins and neuroligins to modulate synaptic cell adhesion in neurons. [5] [6] As the name implies, its protein product is a transmembrane protein that contains many leucine rich repeats. It is expressed during the development of specific forebrain structures and shows a variable pattern of maternal downregulation (genomic imprinting). [7] [8]
LRRTM1 is the first gene linked to increased odds of being left-handed, when inherited from the father's side. [9] Possessing one particular variant of the LRRTM1 gene slightly raises the risk of psychotic mental illnesses such as schizophrenia, again only if inherited from the father's side. [9] As well, LRRTM1 has been associated with measures of schizotypy in non-clinical populations, [10] indicating that the gene may have shared effects on neurodevelopment in both healthy and unhealthy individuals and individuals with schizophrenia.
LRRTM1 is also critically involved in synapse formation within the dorsal lateral geniculate nucleus (dLGN) of mice. LRRTM1 aids in the assembly of complex retinogeniculate synapses in mice, which are believed to help process complex visual signals. Lack of this gene shows decreased performance in complex visual tasks. [11]
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 interacts with proteins in the synaptic cleft, most notably neuroligin, while the intracellular cytoplasmic portion interacts with proteins associated with exocytosis. Neurexin and neuroligin "shake hands," resulting in the connection between the two neurons and the production of a synapse. Neurexins mediate signaling across the synapse, and influence the properties of neural networks by synapse specificity. Neurexins were discovered as receptors for α-latrotoxin, a vertebrate-specific toxin in black widow spider venom that binds to presynaptic receptors and induces massive neurotransmitter release. In humans, alterations in genes encoding neurexins are implicated in autism and other cognitive diseases, such as Tourette syndrome and schizophrenia.
Peripheral plasma membrane protein CASK is a protein that in humans is encoded by the CASK gene. This gene is also known by several other names: CMG 2, calcium/calmodulin-dependent serine protein kinase 3 and membrane-associated guanylate kinase 2. CASK gene mutations are the cause of XL-ID with or without nystagmus and MICPCH, an X-linked neurological disorder.
Leucine-rich repeat-containing G-protein coupled receptor 4 is a protein that in humans is encoded by the LGR4 gene. LGR4 is known to have a role in the development of the male reproductive tract, eyelids, hair and bone.
Leucine-rich repeat-containing G-protein coupled receptor 6 is a protein that in humans is encoded by the LGR6 gene. Along with the other G-protein coupled receptors LGR4 and LGR5, LGR6 is a Wnt signaling pathway mediator. LGR6 also acts as an epithelial stem cell marker in squamous cell carcinoma in mice in vivo.
Neurexin-1-alpha is a protein that in humans is encoded by the NRXN1 gene.
Neuroligin-3 is a protein that in humans is encoded by the NLGN3 gene.
Neuroligin-4, X-linked is a protein that in humans is encoded by the NLGN4X gene.
Neuroligin-1 is a protein that in humans is encoded by the NLGN1 gene.
Neurexin-2-alpha is a protein that in humans is encoded by the NRXN2 gene.
Leucine-rich repeats and immunoglobulin-like domains protein 1 is a protein that in humans is encoded by the LRIG1 gene. It encodes a transmembrane protein that has been shown to interact with receptor tyrosine kinases of the EGFR family and with MET and RET.
Leucine rich repeat containing 7 also known as LRRC7, Densin-180, or LAP1 is a protein which in humans is encoded by the LRRC7 gene.
Receptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the PTPRT gene.
Neuroligin-2 is a protein that in humans is encoded by the NLGN2 gene.
Leucine-rich repeat and Immunoglobulin-like domain-containing protein 1 also known as LINGO-1 is a protein which is encoded by the LINGO1 gene in humans. It belongs to the family of leucine-rich repeat proteins which are known for playing key roles in the biology of the central nervous system. LINGO-1 is a functional component of the Nogo receptor also known as the reticulon 4 receptor.
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 adhesion proteins located presynaptically. Neuroligin and β-neurexin "shake hands", resulting in the connection between two neurons and the production of a synapse. Neuroligins also affect the properties of neural networks by specifying synaptic functions, and they mediate signalling by recruiting and stabilizing key synaptic components. Neuroligins interact with other postsynaptic proteins to localize neurotransmitter receptors and channels in the postsynaptic density as the cell matures. Additionally, neuroligins are expressed in human peripheral tissues and have been found to play a role in angiogenesis. In humans, alterations in genes encoding neuroligins are implicated in autism and other cognitive disorders. Antibodies in a mother from previous male pregnancies against neuroligin 4 from the Y chromosome increase the probability of homosexuality in male offspring.
Leucine-rich repeat neuronal protein 2 is a protein that in humans is encoded by the LRRN2 gene.
Leucine-rich repeat transmembrane protein FLRT3 is a protein that in humans is encoded by the FLRT3 gene.
Leucine rich repeat containing 24 is a protein that, in humans, is encoded by the LRRC24 gene. The protein is represented by the official symbol LRRC24, and is alternatively known as LRRC14OS. The function of LRRC24 is currently unknown. It is a member of the leucine-rich repeat (LRR) superfamily of proteins.
Leucine-rich repeat-containing protein 8C is a protein that in humans is encoded by the LRRC8C gene. Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8B, LRRC8D, and LRRC8E, is sometimes a subunit of the heteromer protein Volume-Regulated Anion Channel. Volume-Regulated Anion Channels (VRACs) are crucial to the regulation of cell size by transporting chloride ions and various organic osmolytes, such as taurine or glutamate, across the plasma membrane, and that is not the only function these channels have been linked to.
Synaptic stabilization is crucial in the developing and adult nervous systems and is considered a result of the late phase of long-term potentiation (LTP). The mechanism involves strengthening and maintaining active synapses through increased expression of cytoskeletal and extracellular matrix elements and postsynaptic scaffold proteins, while pruning less active ones. For example, cell adhesion molecules (CAMs) play a large role in synaptic maintenance and stabilization. Gerald Edelman discovered CAMs and studied their function during development, which showed CAMs are required for cell migration and the formation of the entire nervous system. In the adult nervous system, CAMs play an integral role in synaptic plasticity relating to learning and memory.
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