Dataset Information

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.

SUBMITTER: Kegel L

PROVIDER: S-EPMC3691968 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LGI proteins in the nervous system.

Kegel Linde L Aunin Eerik E Meijer Dies D Bermingham John R JR

ASN neuro 20130625 3

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 interaction ...[more]

PMID: 23713523

Similar Datasets

Project description:Proteins encoded by transposable elements (TEs) play a vital role in their proliferation in host genomes. In recent years, an increasing number of studies have shown that TE proteins have contributed to the emergence of novel host proteins. In Drosophila, there are several proteins derived from the PIF/Harbinger transposase superfamily called Drosophila PIF Like Genes (DPLGs). Here, we investigated the function of four DPLGs (DPLG1-4) in D. melanogaster that are highly conserved and present across Drosophila but are deeply diverged from each other, and likely originated through independent domestication of the transposase from distinct PIF-like TE families. We have analyzed transcript localization of DPLG 1-4, tagged DPLG3 and DPLG4 and studied their protein localization and, produced null alleles for DPLG1 and DPLG4. RNA in situ hybridization reveals that DPLG1-4 have strikingly similar pattern of transcript localization in the gonads, and in the nervous system during embryogenesis, suggesting their domestication for related functions. DPLGs show co-expression enrichment with transcription factors in ovaries and during embryogenesis supporting that they may be domesticated as regulatory proteins in flies. DPLG3 and DPLG4 tagged proteins localize with DNA in the nucleus of the ovaries consistent with this hypothesis. Loss of DPLG1 or DPLG4 results in viability and/or fertility effects, while loss of both DPLG1 and DPLG4 resulted in no effect in viability or fertility suggesting genetic interaction between these two genes. Further, loss of DPLG4 showed increased survival in flies, and increased fertility in older females indicating its involvement in the process of ageing. Transcriptional analyses in the ovaries showed that the loss of either DPLG1 or DPLG4 protein leads to modest changes in transcription of a large and significantly overlapping set of genes, and also affects transposable elements activity. The observed functional overlap of independently domesticated transposases from the same TE family and genetic interaction between them suggests a stepping stone model in which domestication of a PIF/Harbinger transposase might promote the domestication of related transposases for gonad and nervous system regulatory functions.

Dataset Information

LGI proteins in the nervous system.

Publications

LGI proteins in the nervous system.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure