FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2231666828> ?p ?o ?g. }

• W2231666828 abstract "This chapter presents recent works on Myocloni1/ EFHC1 a protein encoded by an epilepsy causing gene of juvenile myoclonic epilepsy (JME), one of the most frequent forms of idiopathic or genetic generalized epilepsies. Myoclonin 1/EFHC1 is a microtubule-associated protein involved in the regulation of cell division. In vitro, EFHC1 loss of function disrupted mitotic spindle organization, impaired M phase progression, induced microtubule bundling and increased apoptosis. EFHC1 impairment in the rat developing neocortex by ex vivo and in utero electroporation caused a marked disruption of radial migration. This effect was a result of cortical progenitors failing to exit the cell cycle. On the other hand, defects in the radial glia scaffold organization and in the locomotion of postmitotic neurons. Mutant analysis of Defhc1 lossand gain-of-function alleles in vivo in Drosophila revealed a number of neuronal defects, including abnormal synaptic development characterized by extensive satellite bouton formation, increased frequency of spontaneous neurotransmitter release, and aberrations in dendritic arbour morphogenesis. Thus, Myoclonin 1/ EFHC1 is a regulator of cell division and neuronal migration during cortical development synaptic bouton and dendritic morphogenesis. Disruption of these properties lead to JME, being now therefore considered as a developmental disease. Juvenile myoclonic epilepsy (JME) is the most frequent form of idiopathic/genetic generalized epilepsy. It accounts for 2–12 % of all epilepsies. JME symptoms of myoclonias and tonicclonic convulsions appear in adolescence in an otherwise normal person with normal neurological and cognitive functions (Delgado-Escueta and Bacsal, 1984)1. Five percent of these patients, five percent of their affected family members and eight percent of a 252 patient Corresponding author : Prof Thierry GRISAR, MD,PhD, University of Liege, GIGA Neuroscience Blvd de l’Hopital 1, 4000 Liege BELGIUM e-mail : tgrisar@ulg.ac.be. Japer's Basic M ecanism s of he Eppsies Japer's Basic M ecanism s of he Eppsies cohort followed for over 20 years only have seizures when triggered by external factors such as alcohol use, fatigue, menstruation and sleep deprivation. To understand the disease mechanisms underlying the stages of susceptibility and epileptogenesis in JME, many have tried to define its complex heritability and identify the genes corresponding to the fifteen chromosomal loci so far linked to the disease2 (see also chapter ...in this book). In 2004, Suzuki et al. identified several heterozygous missense mutations in a gene called EFHC1 3 in different unrelated families with JME probands. Since then, heterozygous non sense, deletion frame shifts and novel missense mutations have been identified in various populations of Italy, Austria and Chile 4–7 .Nine percent of sporadic JME cases detected in families consecutively seen in epilepsy clinics of Mexico and Honduras and 3 % of clinic patients from Japan carry mutations in EFHC1. This represents the highest number and percentage of mutations found for a juvenile myoclonic epilepsy causing gene of any population group 7. The gene encodes a 75-kDa protein with three DM10 domains of unknown function and a single EF-hand motif, a Ca2+-binding domain. The transcript is observed in many cell type of human tissue including brain (in particular in ependymal or periventricular cells) but also best expressed in dividing cells with highest levels in lung and testis 3. It was first proposed that EFHC1 was “pro-apoptotic” when overexpression in hippocampal neurons in vitro induced apoptotic cell death. This effect was significantly reduced by any of the five mutations associated with JME. Patch-clamp analysis of BHK (Baby Hamster Kidney) cells transfected with Cav2.3 VDCC (voltage-dependent calcium channel) and EFHC1 showed significantly increased R-type Ca2+ currents. So, the pro-apoptotic effect of EFHC1 was assigned to this enhancing effect on Ca2+ through Cav2.3 VDCC 3. In 2005, another research group pointed out that EFHC1 is orthologous to Rib72, an axonemal protein of Chlamydomonas reinhardtii. They demonstrated that EFHC1 is abundantly expressed in mouse tissues that have motile cilia or flagella, including the brain, and suggested that it plays a role in the intrinsic properties of these organelles 8. One of our laboratories previously reported that the subcellular distribution of EFHC1 in different cell lines varied during the cell cycle. In interphase cells, the protein is present in the cytoplasm and nucleus, except nucleoli and is particularly concentrated at the centrosome. During mitosis, EFHC1 is localized at spindle poles of the mitotic spindle and also at the midbody during cytokinesis 9. These results suggest that EFHC1 could play an important role during cell division and in particular during brain development since mRNA expression is higher at embryonic stages as compared to adult 10. More recently, we demonstrated that EFHC1 is a microtubule-associated protein (MAP) playing a key role in neuronal migration 11. In this chapter we review these putative roles of Myoclonin 1 / EFHC1 or during brain development and during adulthood. We posit an hypothesis that JME is a developmental disease involving neuronal migration and synaptic bouton and dendritic morphogenesis. EFHC1/MYOCLONIN1, A PROTEIN OF UNKNOWN FUNCTION Myoclonin 1 /EFHC1 gene is located on chromosome 6 (6p11–12) between markers D6S1960 and D6S11024, spans 72 kb and contains 11 exons. This gene encodes a protein of 640 amino acids. A domain search identified three tandemly repeated so called DM10 domains, a motif with unknown function. This protein also contains a single EF-hand, a well known Ca2+binding motif, from which it was named EFHC1 for EF-hand Containing 1 (Figure 1). This motif is located at the C-terminus between amino acid 578 and 606 and encoded by a nucleotide sequence present in exon 10. Page 2 Myoclonin1/EFHC1 in cell division, neuroblast migration, synapse/dendrite formation in juvenile myoclonic epilepsy Japer's Basic M ecanism s of he Eppsies Japer's Basic M ecanism s of he Eppsies Figure 1. Schematic representation of the EFHC1/Myoclonin1 gene, the long and short forms of the EFHC1 protein and the different mutations found co segregated with the JME phenotype The transcript undergo alternative splicing in exon 4, resulting in a C-terminally truncated protein, eliminating the EF-hand domain and two DM10 sequences. This last short form therefore only contains 278 amino acids, the first 240 being common with the entire molecule." @default.
• W2231666828 created "2016-06-24" @default.
• W2231666828 creator A5010621919 @default.
• W2231666828 creator A5021002044 @default.
• W2231666828 creator A5026317578 @default.
• W2231666828 creator A5044458916 @default.
• W2231666828 creator A5063311010 @default.
• W2231666828 creator A5069790998 @default.
• W2231666828 date "2012-01-01" @default.
• W2231666828 modified "2023-09-27" @default.
• W2231666828 title "Myoclonin1/EFHC1 in cell division, neuroblast migration, synapse/dendrite formation in juvenile myoclonic epilepsy" @default.
• W2231666828 cites W1487547430 @default.
• W2231666828 cites W1571243084 @default.
• W2231666828 cites W1614264721 @default.
• W2231666828 cites W1965608446 @default.
• W2231666828 cites W1966685408 @default.
• W2231666828 cites W1969971056 @default.
• W2231666828 cites W1970901705 @default.
• W2231666828 cites W1971002207 @default.
• W2231666828 cites W1972352530 @default.
• W2231666828 cites W1972880385 @default.
• W2231666828 cites W1973232667 @default.
• W2231666828 cites W1973262048 @default.
• W2231666828 cites W1977594779 @default.
• W2231666828 cites W1981941572 @default.
• W2231666828 cites W1987085702 @default.
• W2231666828 cites W1989993507 @default.
• W2231666828 cites W1998053277 @default.
• W2231666828 cites W1999534125 @default.
• W2231666828 cites W2000953432 @default.
• W2231666828 cites W2005864888 @default.
• W2231666828 cites W2005935748 @default.
• W2231666828 cites W2006628753 @default.
• W2231666828 cites W2006781041 @default.
• W2231666828 cites W2007783997 @default.
• W2231666828 cites W2011537456 @default.
• W2231666828 cites W2017585266 @default.
• W2231666828 cites W2018075425 @default.
• W2231666828 cites W2021981560 @default.
• W2231666828 cites W2025191441 @default.
• W2231666828 cites W2025714675 @default.
• W2231666828 cites W2032569108 @default.
• W2231666828 cites W2035106298 @default.
• W2231666828 cites W2037799994 @default.
• W2231666828 cites W2039246157 @default.
• W2231666828 cites W2041619316 @default.
• W2231666828 cites W2042669262 @default.
• W2231666828 cites W2048443355 @default.
• W2231666828 cites W2049225918 @default.
• W2231666828 cites W2058549524 @default.
• W2231666828 cites W2059628826 @default.
• W2231666828 cites W2059987115 @default.
• W2231666828 cites W2066232525 @default.
• W2231666828 cites W2077630079 @default.
• W2231666828 cites W2078564581 @default.
• W2231666828 cites W2080893376 @default.
• W2231666828 cites W2083689477 @default.
• W2231666828 cites W2084343784 @default.
• W2231666828 cites W2090874391 @default.
• W2231666828 cites W2104520647 @default.
• W2231666828 cites W2105593651 @default.
• W2231666828 cites W2105712639 @default.
• W2231666828 cites W2111920698 @default.
• W2231666828 cites W2112661254 @default.
• W2231666828 cites W2120215029 @default.
• W2231666828 cites W2124386744 @default.
• W2231666828 cites W2127183070 @default.
• W2231666828 cites W2133591190 @default.
• W2231666828 cites W2135427218 @default.
• W2231666828 cites W2135819044 @default.
• W2231666828 cites W2137220579 @default.
• W2231666828 cites W2142546000 @default.
• W2231666828 cites W2150180767 @default.
• W2231666828 cites W2154665940 @default.
• W2231666828 cites W2169403700 @default.
• W2231666828 cites W2417314073 @default.
• W2231666828 cites W2611359269 @default.
• W2231666828 hasPublicationYear "2012" @default.
• W2231666828 type Work @default.
• W2231666828 sameAs 2231666828 @default.
• W2231666828 citedByCount "0" @default.
• W2231666828 crossrefType "journal-article" @default.
• W2231666828 hasAuthorship W2231666828A5010621919 @default.
• W2231666828 hasAuthorship W2231666828A5021002044 @default.
• W2231666828 hasAuthorship W2231666828A5026317578 @default.
• W2231666828 hasAuthorship W2231666828A5044458916 @default.
• W2231666828 hasAuthorship W2231666828A5063311010 @default.
• W2231666828 hasAuthorship W2231666828A5069790998 @default.
• W2231666828 hasConcept C127445978 @default.
• W2231666828 hasConcept C169760540 @default.
• W2231666828 hasConcept C2524010 @default.
• W2231666828 hasConcept C2777222312 @default.
• W2231666828 hasConcept C2778186239 @default.
• W2231666828 hasConcept C2779814861 @default.
• W2231666828 hasConcept C33923547 @default.
• W2231666828 hasConcept C84248122 @default.
• W2231666828 hasConcept C86803240 @default.
• W2231666828 hasConcept C93304396 @default.
• W2231666828 hasConcept C95444343 @default.
• W2231666828 hasConceptScore W2231666828C127445978 @default.

• next