EFHC1, a protein mutated in juvenile myoclonic epilepsy, associates with the mitotic spindle through its N-terminus

Nijs, Laurence de; Lakaye, Bernard; Coumans, Bernard; Léon, Christine; Ikeda, Takashi; Delgado‐Escueta, Antonio V.; Grisar, Thierry; Chanas, Grazyna

doi:10.1016/j.yexcr.2006.05.011

Cited by 32 publications

(23 citation statements)

References 27 publications

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“…Then, we studied the distribution of the protein in the brain using a previously validated purified polyclonal antibody against EFHC1 (Ikeda et al, 2005;de Nijs et al, 2006). In agreement with the mRNA distribution, we observed protein expression in many adult brain structures.…”

Section: Discussionsupporting

confidence: 61%

“…The distribution and cellular localization of EFHC1 in adult mouse brain were then studied by immunohistochemistry using a previously well validated anti-EFHC1 antibody (Ikeda et al, 2005;de Nijs et al, 2006). In the adult mouse neocortex, the labeling was present in cells of all cortical layers (Fig.…”

Section: Efhc1 Protein Is Detected In Brain Of E16 Mice Embryos and Amentioning

confidence: 99%

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Distribution of EFHC1 or Myoclonin 1 in mouse neural structures

et al. 2010

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Summary EFHC1, a gene mutated in juvenile myoclonic epilepsy, encodes EFHC1, a protein with three DM10 domains and one EF-hand motif. We recently demonstrated that this molecule is a microtubule-associated protein (MAP) implicated in neuronal migration. Because some controversies persist about the precise localization in the CNS, we studied the neuroanatomical distribution of EFHC1 in mature and developing mouse brain. In the adult, low mRNA expression was detected in several brain structures such as cortex, striatum, hippocampus and cerebellum. At E16, EFHC1 mRNA was shown to be expressed in cortex and not only in cells lining ventricles.Using a purified polyclonal antibody, EFHC1 staining was observed in all cortical layers, in piriform cortex, in hippocampus and in Purkinje cells of cerebellum. In the cortex, the majority of EFHC1 positive cells correspond to neurons, however some glial cells were also stained. In agreement with a previous study, we demonstrated strong EFHC1 expression in cilia of ependymal cells lining cerebral ventricles. Moreover, at E16, the protein was observed at the borders of brain ventricles, in choroid plexus, but also, although to a lesser extent, in piriform and neocortex. In these latter structures, the pattern of expression seems to correspond to the extensions of the radial glia fibers as demonstrated by BLBP immunostaining. Finally, we confirmed that EFHC1 was also expressed and co-localized with the mitotic spindle of neural stem cells.These results confirm that EFHC1 is a protein with a likely low expression level in mouse brain but detectable both in adult and embryonic brain supporting our previous data and Abbreviations: ABC, avidin-biotin-peroxidase complex; BLBP, brain lipid-binding protein; DAB3, 3 -diaminobenzidine; FITC, fluorescein isothiocyanate; GFAP, glial fibrillary acidic protein; IgG, immunoglobulin G; JME, juvenile myoclonic epilepsy; MAP, microtubule-associated protein; MTOC, microtubule-organizing center; NeuN, neuronal nuclei; NGS, normal goat serum; NSC, neural stem cells; PBS, phosphatebuffered saline; PBSG, phosphate-buffered saline with 4.5 g/l glucose; PFA, paraformaldehyde; RRX, rhodamine Red-X; VDCC, voltagedependent calcium channel. Distribution of EFHC1 or Myoclonin 1 in mouse neural structures 197 hypothesis that EFHC1 could play an important role during brain development. As discussed, this opens the door to a new conceptual approach viewing some idiopathic generalized epilepsies as developmental diseases instead of classical channelopathies.

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Section: Discussionsupporting

confidence: 61%

Section: Efhc1 Protein Is Detected In Brain Of E16 Mice Embryos and Amentioning

confidence: 99%

Distribution of EFHC1 or Myoclonin 1 in mouse neural structures

et al. 2010

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“…So, it is possible that EFHC1 participates in ciliary function. In addition, there is a growing body of evidences suggesting that EFHC1 plays this role by the interaction with microtubules (Ikeda et al 2005;de Nijs et al 2006). The importance of microtubules in neuronal migration was the subject of many studies (Hafezparast et al 2003;Tanaka et al 2004) and it has been emphasized by the demonstration that mutations in α-tubulin cause abnormalities in this process (Keays et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Expression Profile and Distribution of Efhc1 Gene Transcript During Rodent Brain Development

et al. 2009

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One of the putative causative genes for juvenile myoclonic epilepsy (JME) is EFHC1. We report here the expression profile and distribution of Efhc1 messenger RNA (mRNA) during mouse and rat brain development. Real-time polymerase chain reaction revealed that there is no difference in the expression of Efhc1 mRNA between right and left hemispheres in both species. In addition, the highest levels of Efhc1 mRNA were found at intra-uterine stages in mouse and in adulthood in rat. In common, there was a progressive decrease in Efhc1 expression from 1-day-old neonates to 14-day-old animals in both species. In situ hybridization studies showed that rat and mouse Efhc1 mRNAs are expressed in ependymal cells of ventricle walls. Our findings suggest that Efhc1 expression is more important during initial phases of brain development and that at this stage it could be involved in key developmental mechanisms underlying JME.

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“…Ciliary/flagellar central pair singlet microtubules contain labile pf-ribbons [17,46,66], they stain weakly with affinity-purified, monospecific antitektin C antibodies [40], and they possess 16-and 32-nm periodic structures [5,70,78]. Furthermore, anti-tektin antibodies stain singlet mitotic midbody microtubules [89], and GPF-tagged efhc1 localizes to them [90]. Tektins are also components of centrioles and basal bodies [40,[42][43][44]91].…”

Section: A Super-coil Model For Tektin Interactions and Axoneme Strucmentioning

confidence: 99%