The Experts below are selected from a list of 5460 Experts worldwide ranked by ideXlab platform
Sachiko Tsukita - One of the best experts on this subject based on the ideXlab platform.
-
Dysregulation of lung injury and repair in moesin-deficient mice treated with intratracheal bleomycin.
American journal of physiology. Lung cellular and molecular physiology, 2008Co-Authors: Soshi Hashimoto, Shojiro Kikuchi, Fumimasa Amaya, Hiroki Matsuyama, Hiroshi Ueno, Masaki Tanaka, Yoshihisa Watanabe, Masahito Ebina, Akitoshi Ishizaka, Sachiko TsukitaAbstract:Moesin belongs to the ezrin/Radixin/moesin (ERM) protein family and participates in cellular functions, such as morphogenesis and motility, by cross-linking between the actin cytoskeleton and plasm...
-
Activated Radixin is essential for GABAA receptor α5 subunit anchoring at the actin cytoskeleton
The EMBO journal, 2006Co-Authors: Sven Loebrich, Robert Bähring, Tatsuya Katsuno, Sachiko Tsukita, Matthias KneusselAbstract:Neurotransmitter receptor clustering is thought to represent a critical parameter for neuronal transmission. Little is known about the mechanisms that anchor and concentrate inhibitory neurotransmitter receptors in neurons. GABAA receptor (GABAAR) α5 subunits mainly locate at extrasynaptic sites and are thought to mediate tonic inhibition. Notably, similar as synaptic GABAARs, these receptor subtypes also appear in cluster formations at neuronal surface membranes and are of particular interest in cognitive processing. GABAAR α5 mutation or depletion facilitates trace fear conditioning or improves spatial learning in mice, respectively. Here, we identified the actin-binding protein Radixin, a member of the ERM family, as the first directly interacting molecule that anchors GABAARs at cytoskeletal elements. Intramolecular activation of Radixin is a functional prerequisite for GABAAR α5 subunit binding and both depletion of Radixin expression as well as replacement of the Radixin F-actin binding motif interferes with GABAAR α5 cluster formation. Our data suggest Radixin to represent a critical factor in receptor localization and/or downstream signaling.
-
Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia
The Journal of cell biology, 2004Co-Authors: Shin-ichiro Kitajiri, Shoichiro Tsukita, Tatsuya Katsuno, Kanehisa Fukumoto, Masaki Hata, Hiroyuki Sasaki, Takayuki Nakagawa, Juichi Ito, Sachiko TsukitaAbstract:Ezrin/Radixin/moesin (ERM) proteins cross-link actin filaments to plasma membranes to integrate the function of cortical layers, especially microvilli. We found that in cochlear and vestibular sensory hair cells of adult wild-type mice, Radixin was specifically enriched in stereocilia, specially developed giant microvilli, and that Radixin-deficient (Rdx(-)(/)(-)) adult mice exhibited deafness but no obvious vestibular dysfunction. Before the age of hearing onset ( approximately 2 wk), in the cochlea and vestibule of Rdx(-)(/)(-) mice, stereocilia developed normally in which ezrin was concentrated. As these Rdx(-)(/)(-) mice grew, ezrin-based cochlear stereocilia progressively degenerated, causing deafness, whereas ezrin-based vestibular stereocilia were maintained normally in adult Rdx(-)(/)(-) mice. Thus, we concluded that Radixin is indispensable for the hearing ability in mice through the maintenance of cochlear stereocilia, once developed. In Rdx(-)(/)(-) mice, ezrin appeared to compensate for Radixin deficiency in terms of the development of cochlear stereocilia and the development/maintenance of vestibular stereocilia. These findings indicated the existence of complicate functional redundancy in situ among ERM proteins.
-
Structural conversion between open and closed forms of Radixin: low-angle shadowing electron microscopy.
Journal of molecular biology, 2001Co-Authors: Hiroaki Ishikawa, Toshio Hakoshima, Takeshi Matsui, Shoichiro Tsukita, Hiroyuki Sasaki, Atsushi Tamura, Sachiko TsukitaAbstract:Abstract The function of ERM (ezrin/Radixin/moesin) proteins as general cross-linkers between actin filaments and plasma membranes is regulated downstream of Rho, through the transition between active and inactive forms. To directly examine the conformational change between the active and inactive forms of ERM proteins, we applied low-angle rotary-shadowing electron microscopy to the Radixin molecules, wild-type, T564A-non-phosphorylated-type, and T564E-phosphorylated-type, since most of the active forms are reportedly stabilized in cells by the C-terminal threonine phosphorylation. As a result, the T564A- and wild-type Radixin molecules yielded the globular closed forms, ∼8-14 nm in diameter, with some striations on their surfaces. In contrast, the T564E-Radixin molecules tended to take elongated open forms, in which two globular structures measuring ∼8 nm and ∼5 nm in diameter were associated with both ends of the filamentous structures. The filamentous structure took either a ∼20-25 nm-long straight course or a folded course. Taken together with the biochemical and the crystal structural results obtained to date, the closed and open forms represent the inactive and active forms of Radixin as cross-linkers between actin filaments and plasma membranes.
-
Expression level, subcellular distribution and Rho-GDI binding affinity of merlin in comparison with ezrin/Radixin/moesin proteins
Oncogene, 1999Co-Authors: Masato Maeda, Takeshi Matsui, Shoichiro Tsukita, Masayuki Imamura, Sachiko TsukitaAbstract:Expression level, subcellular distribution and Rho-GDI binding affinity of merlin in comparison with ezrin/Radixin/moesin proteins
Shoichiro Tsukita - One of the best experts on this subject based on the ideXlab platform.
-
Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia
The Journal of cell biology, 2004Co-Authors: Shin-ichiro Kitajiri, Shoichiro Tsukita, Tatsuya Katsuno, Kanehisa Fukumoto, Masaki Hata, Hiroyuki Sasaki, Takayuki Nakagawa, Juichi Ito, Sachiko TsukitaAbstract:Ezrin/Radixin/moesin (ERM) proteins cross-link actin filaments to plasma membranes to integrate the function of cortical layers, especially microvilli. We found that in cochlear and vestibular sensory hair cells of adult wild-type mice, Radixin was specifically enriched in stereocilia, specially developed giant microvilli, and that Radixin-deficient (Rdx(-)(/)(-)) adult mice exhibited deafness but no obvious vestibular dysfunction. Before the age of hearing onset ( approximately 2 wk), in the cochlea and vestibule of Rdx(-)(/)(-) mice, stereocilia developed normally in which ezrin was concentrated. As these Rdx(-)(/)(-) mice grew, ezrin-based cochlear stereocilia progressively degenerated, causing deafness, whereas ezrin-based vestibular stereocilia were maintained normally in adult Rdx(-)(/)(-) mice. Thus, we concluded that Radixin is indispensable for the hearing ability in mice through the maintenance of cochlear stereocilia, once developed. In Rdx(-)(/)(-) mice, ezrin appeared to compensate for Radixin deficiency in terms of the development of cochlear stereocilia and the development/maintenance of vestibular stereocilia. These findings indicated the existence of complicate functional redundancy in situ among ERM proteins.
-
Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes
Nature genetics, 2002Co-Authors: Shojiro Kikuchi, Takeshi Matsui, Shigenobu Yonemura, Dietrich Keppler, Kanehisa Fukumoto, Masaki Hata, Atsushi Tamura, Yukari Yamane, Hisakazu Yamagishi, Shoichiro TsukitaAbstract:The ezrin-Radixin-moesin (ERM) family of proteins crosslink actin filaments and integral membrane proteins. Radixin (encoded by Rdx) is the dominant ERM protein in the liver of wildtype mice and is concentrated at bile canalicular membranes (BCMs). Here we show that Rdx(-/-) mice are normal at birth, but their serum concentrations of conjugated bilirubin begin to increase gradually around 4 weeks, and they show mild liver injury after 8 weeks. This phenotype is similar to human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury. In wildtype mice, Mrp2 concentrates at BCMs to secrete conjugated bilirubin into bile. In the BCMs of Rdx(-/-) mice, Mrp2 is decreased compared with other BCM proteins such as dipeptidyl peptidase IV (CD26) and P-glycoproteins. In vitro binding studies show that Radixin associates directly with the carboxy-terminal cytoplasmic domain of human MRP2. These findings indicate that Radixin is required for secretion of conjugated bilirubin through its support of Mrp2 localization at BCMs.
-
Structural conversion between open and closed forms of Radixin: low-angle shadowing electron microscopy.
Journal of molecular biology, 2001Co-Authors: Hiroaki Ishikawa, Toshio Hakoshima, Takeshi Matsui, Shoichiro Tsukita, Hiroyuki Sasaki, Atsushi Tamura, Sachiko TsukitaAbstract:Abstract The function of ERM (ezrin/Radixin/moesin) proteins as general cross-linkers between actin filaments and plasma membranes is regulated downstream of Rho, through the transition between active and inactive forms. To directly examine the conformational change between the active and inactive forms of ERM proteins, we applied low-angle rotary-shadowing electron microscopy to the Radixin molecules, wild-type, T564A-non-phosphorylated-type, and T564E-phosphorylated-type, since most of the active forms are reportedly stabilized in cells by the C-terminal threonine phosphorylation. As a result, the T564A- and wild-type Radixin molecules yielded the globular closed forms, ∼8-14 nm in diameter, with some striations on their surfaces. In contrast, the T564E-Radixin molecules tended to take elongated open forms, in which two globular structures measuring ∼8 nm and ∼5 nm in diameter were associated with both ends of the filamentous structures. The filamentous structure took either a ∼20-25 nm-long straight course or a folded course. Taken together with the biochemical and the crystal structural results obtained to date, the closed and open forms represent the inactive and active forms of Radixin as cross-linkers between actin filaments and plasma membranes.
-
Crystallographic characterization of the Radixin FERM domain bound to the cytoplasmic tail of the adhesion protein ICAM-2.
Acta crystallographica. Section D Biological crystallography, 2001Co-Authors: K Hamada, Shoichiro Tsukita, T Shimizu, T Matsui, Toshio HakoshimaAbstract:Radixin is a member of the ERM proteins, which cross-link plasma membranes and actin filaments. The FERM domains located at the N-terminal regions of ERM proteins are responsible for membrane association through direct interactions with the cytoplasmic domains of integral membrane proteins. Here, crystals of the complex between the Radixin FERM domain and the full-length cytoplasmic tail (28-residue peptide) of intercellular adhesion molecule 2, ICAM-2, have been obtained. The crystals were found to belong to space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 100.44 (9), c = 99.49 (6) A, and contain one complex in the crystallographic asymmetric unit. An intensity data set was collected to a resolution of 2.60 A.
-
structural basis of the membrane targeting and unmasking mechanisms of the Radixin ferm domain
The EMBO Journal, 2000Co-Authors: Keisuke Hamada, Takeshi Matsui, Toshiyuki Shimizu, Shoichiro Tsukita, Toshio HakoshimaAbstract:Radixin is a member of the ezrin/Radixin/moesin (ERM) family of proteins, which play a role in the formation of the membrane-associated cytoskeleton by linking actin filaments and adhesion proteins. This cross-linking activity is regulated by phosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP2) in the downstream of the small G protein Rho. The X-ray crystal structures of the Radixin FERM domain, which is responsible for membrane binding, and its complex with inositol-(1,4,5)-trisphosphate (IP3) have been determined. The domain consists of three subdomains featuring a ubiquitin-like fold, a four-helix bundle and a phosphotyrosine-binding-like domain, respectively. These subdomains are organized by intimate interdomain interactions to form characteristic grooves and clefts. One such groove is negatively charged and so is thought to interact with basic juxta-membrane regions of adhesion proteins. IP3 binds a basic cleft that is distinct from those of pleckstrin homology domains and is located on a positively charged flat molecular surface, suggesting an electrostatic mechanism of plasma membrane targeting. Based on the structural changes associated with IP3 binding, a possible unmasking mechanism of ERM proteins by PIP2 is proposed.
Takeshi Matsui - One of the best experts on this subject based on the ideXlab platform.
-
Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes
Nature genetics, 2002Co-Authors: Shojiro Kikuchi, Takeshi Matsui, Shigenobu Yonemura, Dietrich Keppler, Kanehisa Fukumoto, Masaki Hata, Atsushi Tamura, Yukari Yamane, Hisakazu Yamagishi, Shoichiro TsukitaAbstract:The ezrin-Radixin-moesin (ERM) family of proteins crosslink actin filaments and integral membrane proteins. Radixin (encoded by Rdx) is the dominant ERM protein in the liver of wildtype mice and is concentrated at bile canalicular membranes (BCMs). Here we show that Rdx(-/-) mice are normal at birth, but their serum concentrations of conjugated bilirubin begin to increase gradually around 4 weeks, and they show mild liver injury after 8 weeks. This phenotype is similar to human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury. In wildtype mice, Mrp2 concentrates at BCMs to secrete conjugated bilirubin into bile. In the BCMs of Rdx(-/-) mice, Mrp2 is decreased compared with other BCM proteins such as dipeptidyl peptidase IV (CD26) and P-glycoproteins. In vitro binding studies show that Radixin associates directly with the carboxy-terminal cytoplasmic domain of human MRP2. These findings indicate that Radixin is required for secretion of conjugated bilirubin through its support of Mrp2 localization at BCMs.
-
Structural conversion between open and closed forms of Radixin: low-angle shadowing electron microscopy.
Journal of molecular biology, 2001Co-Authors: Hiroaki Ishikawa, Toshio Hakoshima, Takeshi Matsui, Shoichiro Tsukita, Hiroyuki Sasaki, Atsushi Tamura, Sachiko TsukitaAbstract:Abstract The function of ERM (ezrin/Radixin/moesin) proteins as general cross-linkers between actin filaments and plasma membranes is regulated downstream of Rho, through the transition between active and inactive forms. To directly examine the conformational change between the active and inactive forms of ERM proteins, we applied low-angle rotary-shadowing electron microscopy to the Radixin molecules, wild-type, T564A-non-phosphorylated-type, and T564E-phosphorylated-type, since most of the active forms are reportedly stabilized in cells by the C-terminal threonine phosphorylation. As a result, the T564A- and wild-type Radixin molecules yielded the globular closed forms, ∼8-14 nm in diameter, with some striations on their surfaces. In contrast, the T564E-Radixin molecules tended to take elongated open forms, in which two globular structures measuring ∼8 nm and ∼5 nm in diameter were associated with both ends of the filamentous structures. The filamentous structure took either a ∼20-25 nm-long straight course or a folded course. Taken together with the biochemical and the crystal structural results obtained to date, the closed and open forms represent the inactive and active forms of Radixin as cross-linkers between actin filaments and plasma membranes.
-
structural basis of the membrane targeting and unmasking mechanisms of the Radixin ferm domain
The EMBO Journal, 2000Co-Authors: Keisuke Hamada, Takeshi Matsui, Toshiyuki Shimizu, Shoichiro Tsukita, Toshio HakoshimaAbstract:Radixin is a member of the ezrin/Radixin/moesin (ERM) family of proteins, which play a role in the formation of the membrane-associated cytoskeleton by linking actin filaments and adhesion proteins. This cross-linking activity is regulated by phosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP2) in the downstream of the small G protein Rho. The X-ray crystal structures of the Radixin FERM domain, which is responsible for membrane binding, and its complex with inositol-(1,4,5)-trisphosphate (IP3) have been determined. The domain consists of three subdomains featuring a ubiquitin-like fold, a four-helix bundle and a phosphotyrosine-binding-like domain, respectively. These subdomains are organized by intimate interdomain interactions to form characteristic grooves and clefts. One such groove is negatively charged and so is thought to interact with basic juxta-membrane regions of adhesion proteins. IP3 binds a basic cleft that is distinct from those of pleckstrin homology domains and is located on a positively charged flat molecular surface, suggesting an electrostatic mechanism of plasma membrane targeting. Based on the structural changes associated with IP3 binding, a possible unmasking mechanism of ERM proteins by PIP2 is proposed.
-
Crystallographic characterization of the membrane-binding domain of Radixin.
Acta Crystallographica Section D Biological Crystallography, 2000Co-Authors: Keisuke Hamada, Takeshi Matsui, Shoichiro Tsukita, Toshio HakoshimaAbstract:Radixin is a protein which cross-links plasma membranes and actin filaments and thus forms membrane-associated cytoskeleton. The Radixin N-terminal domain, which is responsible for membrane association, has been purified and crystallized by vapour diffusion with polyethylene glycol 6000. The crystals belong to space group P41212 or P43212, with unit-cell parameters a = b = 96.36, c = 133.16 A, and diffract to a resolution of 3.0 A.
-
Crystallographic characterization of the membrane‐binding domain of Radixin
Acta Crystallographica Section D Biological Crystallography, 2000Co-Authors: Keisuke Hamada, Takeshi Matsui, Shoichiro Tsukita, Toshio HakoshimaAbstract:Radixin is a protein which cross-links plasma membranes and actin filaments and thus forms membrane-associated cytoskeleton. The Radixin N-terminal domain, which is responsible for membrane association, has been purified and crystallized by vapour diffusion with polyethylene glycol 6000. The crystals belong to space group P41212 or P43212, with unit-cell parameters a = b = 96.36, c = 133.16 A, and diffract to a resolution of 3.0 A.
Masato Maeda - One of the best experts on this subject based on the ideXlab platform.
-
Expression level, subcellular distribution and Rho-GDI binding affinity of merlin in comparison with ezrin/Radixin/moesin proteins
Oncogene, 1999Co-Authors: Masato Maeda, Takeshi Matsui, Shoichiro Tsukita, Masayuki Imamura, Sachiko TsukitaAbstract:Expression level, subcellular distribution and Rho-GDI binding affinity of merlin in comparison with ezrin/Radixin/moesin proteins
-
expression level subcellular distribution and rho gdi binding affinity of merlin in comparison with ezrin Radixin moesin proteins
Oncogene, 1999Co-Authors: Masato Maeda, Takeshi Matsui, Shoichiro Tsukita, Masayuki Imamura, Sachiko TsukitaAbstract:Expression level, subcellular distribution and Rho-GDI binding affinity of merlin in comparison with ezrin/Radixin/moesin proteins
-
rho kinase phosphorylates cooh terminal threonines of ezrin Radixin moesin erm proteins and regulates their head to tail association
Journal of Cell Biology, 1998Co-Authors: Takeshi Matsui, Sachiko Tsukita, Shigenobu Yonemura, Masato Maeda, Yoshinori Doi, Mutsuki Amano, Kozo Kaibuchi, Shoichiro TsukitaAbstract:The ezrin/Radixin/moesin (ERM) proteins are involved in actin filament/plasma membrane interaction that is regulated by Rho. We examined whether ERM proteins are directly phosphorylated by Rho- associated kinase (Rho-kinase), a direct target of Rho. Recombinant full-length and COOH-terminal half Radixin were incubated with constitutively active catalytic domain of Rho-kinase, and ∼30 and ∼100% of these molecules, respectively, were phosphorylated mainly at the COOH-terminal threonine (T564). Next, to detect Rho-kinase–dependent phosphorylation of ERM proteins in vivo, we raised a mAb that recognized the T564-phosphorylated Radixin as well as ezrin and moesin phosphorylated at the corresponding threonine residue (T567 and T558, respectively). Immunoblotting of serum-starved Swiss 3T3 cells with this mAb revealed that after LPA stimulation ERM proteins were rapidly phosphorylated at T567 (ezrin), T564 (Radixin), and T558 (moesin) in a Rho-dependent manner and then dephosphorylated within 2 min. Furthermore, the T564 phosphorylation of recombinant COOH-terminal half Radixin did not affect its ability to bind to actin filaments in vitro but significantly suppressed its direct interaction with the NH2-terminal half of Radixin. These observations indicate that the Rho-kinase–dependent phosphorylation interferes with the intramolecular and/ or intermolecular head-to-tail association of ERM proteins, which is an important mechanism of regulation of their activity as actin filament/plasma membrane cross-linkers.
-
Rho-Kinase Phosphorylates COOH-terminal Threonines of Ezrin/Radixin/Moesin (ERM) Proteins and Regulates Their Head-to-Tail Association
The Journal of cell biology, 1998Co-Authors: Takeshi Matsui, Sachiko Tsukita, Shigenobu Yonemura, Masato Maeda, Yoshinori Doi, Mutsuki Amano, Kozo Kaibuchi, Shoichiro TsukitaAbstract:The ezrin/Radixin/moesin (ERM) proteins are involved in actin filament/plasma membrane interaction that is regulated by Rho. We examined whether ERM proteins are directly phosphorylated by Rho- associated kinase (Rho-kinase), a direct target of Rho. Recombinant full-length and COOH-terminal half Radixin were incubated with constitutively active catalytic domain of Rho-kinase, and ∼30 and ∼100% of these molecules, respectively, were phosphorylated mainly at the COOH-terminal threonine (T564). Next, to detect Rho-kinase–dependent phosphorylation of ERM proteins in vivo, we raised a mAb that recognized the T564-phosphorylated Radixin as well as ezrin and moesin phosphorylated at the corresponding threonine residue (T567 and T558, respectively). Immunoblotting of serum-starved Swiss 3T3 cells with this mAb revealed that after LPA stimulation ERM proteins were rapidly phosphorylated at T567 (ezrin), T564 (Radixin), and T558 (moesin) in a Rho-dependent manner and then dephosphorylated within 2 min. Furthermore, the T564 phosphorylation of recombinant COOH-terminal half Radixin did not affect its ability to bind to actin filaments in vitro but significantly suppressed its direct interaction with the NH2-terminal half of Radixin. These observations indicate that the Rho-kinase–dependent phosphorylation interferes with the intramolecular and/ or intermolecular head-to-tail association of ERM proteins, which is an important mechanism of regulation of their activity as actin filament/plasma membrane cross-linkers.
Hans Georg Kuhn - One of the best experts on this subject based on the ideXlab platform.
-
Radixin inhibition decreases adult neural progenitor cell migration and proliferation in vitro and in vivo.
Frontiers in cellular neuroscience, 2013Co-Authors: Asa Persson, Olle R Lindberg, Hans Georg KuhnAbstract:Neuronal progenitors capable of long distance migration are produced throughout life in the subventricular zone (SVZ). Migration from the SVZ is carried out along a well-defined pathway called the rostral migratory stream (RMS). Our recent finding of the specific expression of the cytoskeleton linker protein Radixin in neuroblasts suggests a functional role for Radixin in RMS migration. The ezrin-Radixin-moesin (ERM) family of proteins is capable of regulating migration through interaction with the actin cytoskeleton and transmembrane proteins. The ERM proteins are differentially expressed in the RMS with Radixin and moesin localized to neuroblasts, and ezrin expression confined to astrocytes of the glial tubes. Here, we inhibited Radixin function using the quinocarmycin analog DX52-1 which resulted in reduced neuroblast migration in vitro, while glial migration remained unaltered. Furthermore, the morphology of neuroblasts was distorted resulting in a rounded shape with no or short polysialylated neural cell adhesion molecule positive processes. Intracerebroventricular infusion of the Radixin inhibitor resulted in accumulation of neuroblasts in the anterior SVZ. Neuroblast chains were short and intermittently interrupted in the SVZ and considerably disorganized in the RMS. Moreover, we studied the proliferation activity in the RMS after Radixin inhibition, since concentrated Radixin expression has been demonstrated in the cleavage furrow of dividing cells, which indicates a role of Radixin in cell division. Radixin inhibition decreased neuroblast proliferation, whereas the proliferation of other cells in the RMS was not affected. Our results demonstrate a significant role for Radixin in neuroblast proliferation and migration.
-
egf induced expansion of migratory cells in the rostral migratory stream
PLOS ONE, 2012Co-Authors: Olle R Lindberg, Asa Persson, Anke Brederlau, Aidin Shabro, Hans Georg KuhnAbstract:The presence of neural stem cells in the adult brain is currently widely accepted and efforts are made to harness the regenerative potential of these cells. The dentate gyrus of the hippocampal formation, and the subventricular zone (SVZ) of the anterior lateral ventricles, are considered the main loci of adult neurogenesis. The rostral migratory stream (RMS) is the structure funneling SVZ progenitor cells through the forebrain to their final destination in the olfactory bulb. Moreover, extensive proliferation occurs in the RMS. Some evidence suggest the presence of stem cells in the RMS, but these cells are few and possibly of limited differentiation potential. We have recently demonstrated the specific expression of the cytoskeleton linker protein Radixin in neuroblasts in the RMS and in oligodendrocyte progenitors throughout the brain. These cell populations are greatly altered after intracerebroventricular infusion of epidermal growth factor (EGF). In the current study we investigate the effect of EGF infusion on the rat RMS. We describe a specific increase of Radixin+/Olig2+ cells in the RMS. Negative for NG2 and CNPase, these Radixin+/Olig2+ cells are distinct from typical oligodendrocyte progenitors. The expanded Olig2+ population responds rapidly to EGF and proliferates after only 24 hours along the entire RMS, suggesting local activation by EGF throughout the RMS rather than migration from the SVZ. In addition, the Radixin+/Olig2+ progenitors assemble in chains in vivo and migrate in chains in explant cultures, suggesting that they possess migratory properties within the RMS. In summary, these results provide insight into the adaptive capacity of the RMS and point to an additional stem cell source for future brain repair strategies.
-
expression of ezrin Radixin moesin proteins in the adult subventricular zone and the rostral migratory stream
Neuroscience, 2010Co-Authors: A Persson, Maurice A Curtis, Charlotta Lindwall, Hans Georg KuhnAbstract:Abstract Continuous proliferation occurs in the adult subventricular zone (SVZ) of the lateral ventricles throughout life. In the SVZ, progenitor cells differentiate into neuroblasts, which migrate tangentially along the rostral migratory stream (RMS) to reach their final destination in the olfactory bulb. These progenitor cells mature and integrate into the existing neural network of the olfactory bulb. Long distance migration of neuroblasts in the RMS requires a highly dynamic cytoskeleton with the ability to respond to surrounding stimuli. Radixin is a member of the ERM (Ezrin, Radixin, Moesin) family, which connect the actin cytoskeleton to the extracellular matrix through transmembrane proteins. The membrane-cytoskeleton linker proteins of the ERM family may regulate cellular events with a high demand on cytoskeleton plasticity, such as cell motility. Recently, specific expression of the ERM protein ezrin was shown in the RMS. Radixin however has not been characterized in this region. Here we used immunohistochemistry and confocal microscopy to examine the expression of Radixin in the different cell types of the adult subventricular zone niche and in the RMS. Our findings indicate that Radixin is strongly expressed in neuroblasts of the adult RMS and subventricular zone, and also in Olig2-positive cells. We also demonstrate the presence of Radixin in the cerebral cortex, striatum, cerebellum, thalamus, hippocampus as well as the granular and periglomerular layers of the olfactory bulb. Our studies also reveal the localization of Radixin in neurosphere culture studies and we reveal the specificity of our labeling using Western blotting. The expression pattern demonstrated here suggests a role for Radixin in neuronal migration and differentiation in the adult RMS. Understanding how adult neuronal migration is regulated is of importance for the development of new therapeutic interventions using endogenous repair for neurodegenerative diseases.
