title: LGI proteins in the nervous system.
abstract: The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins) play important roles in these processes. They are secreted proteins consisting of an LRR (leucine-rich repeat) domain and a so-called epilepsy-associated or EPTP (epitempin) domain. Both domains are thought to function in protein-protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe) epilepsy) also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions.
authors.affiliation: Department of Genetics and Cell Biology, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Linde
authors.initials: L
authors.lastname: Kegel
authors.forename: Eerik
authors.initials: E
authors.lastname: Aunin
authors.forename: Dies
authors.initials: D
authors.lastname: Meijer
authors.forename: John R
authors.initials: JR
authors.lastname: Bermingham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics; D005075:Biological Evolution; D004285:Dogs; D005910:Glioma / Q000378:metabolism; D006801:Humans; D020363:Limbic Encephalitis / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009420:Nervous System / Q000254:growth & development; D009423:Nervous System Neoplasms / Q000378:metabolism; D009424:Nervous System Physiological Phenomena / Q000235:genetics*; D017933:Peripheral Nervous System / Q000502:physiology; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational / Q000235:genetics; D051381:Rats; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: C555909:Lgi1a protein, zebrafish; D009419:Nerve Tissue Proteins; D029961:Zebrafish Proteins